- The Light Of The Eyelid is the story of a little girl, Sui, who has a strange and apparently incurable disease in her eyes, causing them to become extremely sensitive to light. Despite seeing every doctor her family could find, it reaches the point where even the tiniest amount of light caused her excruciating pain, and she's eventually locked in a storage shed with no windows. Biki, her cousin and Only Friend, visits her every day, brings her food, and plays with her, despite his mother's fears he will contract the disease himself. In his words: "They said it was for Sui's own good that they left her here, but to me, it seemed like they were giving up - like they were abandoning her."
- One day, Sui tells Biki that she already knows the cause of her disease, there are Mushi, mysterious beings and the focus of the series, living in her eyes. She also tells him that when she closes her "second eyelids", she can see a river of light in the otherwise pitch-darkness. When she tries to get closer to the river, a mysterious man warns her not to, that the river isn't safe to look at for long. Meanwhile, Biki's mother's worst fear is realized, as her son catches Sui's illness. The next day, when someone comes to bring Sui her food:Sui: Biki? Biki? What's wrong?Biki's mother: Biki...won't be coming back. He's caught your illness. I know you didn't mean it...It's not your fault. It's my fault for feeling sorry for you.
- After Biki's mother leaves, the light from the river begins to shine brighter around Sui, indicating that she's dangerously close to it. She begins to sink into the light, all the while repeating in an anguished whisper: "Biki... Biki... I'm sorry... I'm sorry..."
- One day, Sui tells Biki that she already knows the cause of her disease, there are Mushi, mysterious beings and the focus of the series, living in her eyes. She also tells him that when she closes her "second eyelids", she can see a river of light in the otherwise pitch-darkness. When she tries to get closer to the river, a mysterious man warns her not to, that the river isn't safe to look at for long. Meanwhile, Biki's mother's worst fear is realized, as her son catches Sui's illness. The next day, when someone comes to bring Sui her food:
- Where Sea Meets Man. Imagine sitting on a beach for two years, watching the sea for some sign of your disappeared wife even as it's clearly hopeless that she's alive. One of the anime's saddest tracks plays when the man finally receives closure about her death.
- The final chapter, Bell Droplets, has several:
- The young, human mountain-master Kaya gives up her life to save Ginko. At the same time she's returned to the life stream, her older brother (who never gave up on her even though she was a weird kid and then went missing for over ten years) hears the sound of bells all over the mountain — the same bells he heard when she was conceived, and knows that she's no longer among the living.
- Her entire ordeal with her family is heartbreaking as well. Because she was born a Mountain Lord, she naturally sought to go out into nature, but her family being her family they wanted to keep their child safe and sound. Her older brother Yoshiro was so heartbroken when she suddenly vanished that he looked for her for years, only to be told by Ginko that she can never go home and to give up searching for her. Even the act of reuniting with her and having her live out a normal life with her estranged family is impossible, as the longer she's away from nature, the more the mountain they live on is thrown into chaos.
- In Clothes That Embrace The Mountain, we are introduced to a man named Kai, who wants to become an artist (much to the disapproval of his father). He finally does leave his small town and, gradually over the course of ten years, makes it big as a wildly popular artist. But after falling into a rut with his work orders piling up, he decides to take a vacation and return to his hometown for a visit. He returns to find the entire town had been buried in a landslide three years before, killing his father among many others. One of the few survivors left, his aunt, reveals that after the disaster his sister sent him a letter requesting help - a letter Kai had burned in the fire without even looking at it, assuming it was yet another work order. It's also revealed Kai's sister died giving birth a year after the landslide, and her young daughter, Toyo, is developmentally slow. Kai decides to raise the girl himself, despite his heavy workload.
- Cushion of Grass: We learn that, because of the Tokoyami mushi, Ginko doesn't remember any part of his life from where Nui was involved and before. Nui was the woman who took Ginko in when his own mother died and explained to him what mushi were for the first time, and she was the most critical event in his life that made him into who he is today. Ginko doesn't remember how he began his lifestyle as a mushishi in the first place. He knows less about himself than the readers do, which isn't much.
- On top of this, there's something sad about the fact that Ginko was so willing to sacrifice himself at the tender age of ten after accidentally breaking the mountain lord's egg. He even questions if he even deserves to live for doing such a thing after the ring of light on the other side of the Light Vein allows him to leave.Ginko: If I...go in there...I probably won't make it back. But I don't care. It's not like I ever belonged anywhere, anyway.
- On top of this, there's something sad about the fact that Ginko was so willing to sacrifice himself at the tender age of ten after accidentally breaking the mountain lord's egg. He even questions if he even deserves to live for doing such a thing after the ring of light on the other side of the Light Vein allows him to leave.
- Aki, the Mama Bear from Cotton Changeling. All she ever wanted was a child, and instead she got afflicted with a mushi that not only produced clones of itself to look like actual children, albeit with strange characteristics such as green hair and abnormal growth rates, but it actually killed her normal fetus in the womb in order to do this. Once Ginko uncovers the truth about the mushi, they try to force themselves into hibernation and disappear by burning down the house with everyone inside. Everyone survives, but poor Aki is left a sobbing wreck in the arms of her husband as they sit, childless once again, outside the burnt remains of what was once their home. Her backstory is depressing too - her husband tells Ginko that she was originally married to a rich merchant, who divorced her after the son and heir she bore him died.
- The ending to The Pillow Pathway. Jin's dreams weren't prophetic at all - in fact, the mushi he was afflicted with were making anything he dreamed into a reality. Anything. And he's never going to be completely rid of it. By the time he figures this out, though, he's already had a dream that's wiped out everyone else in his village. Despite Ginko's attempts to help rid him of the mushi anyway, Jin ultimately loses his mind with guilt, and stabs himself.
- Episode 2 of Zoku-Shou, The Warbling Sea Shell. The ending doubles as heartwarming: the father held a grudge against the village elder for his wife's death by shark attack, causing him to distance himself from the village from that point onward. However, after the red tide occurs and the villagers have nothing to eat, he and his daughter hand the pearl they found over to the elder so the village can feed themselves while they try and recover. Some Manly Tears are shed and the two become a part of the village again, which makes it so that the daughter can finally have friends and speak again and the father can develop closure about his wife's death.
- In the same episode, it's shown that the village elder feels so guilty about the death of the other man's wife that he reorganized the entire village's method of fishing, going to considerable effort to set up fish farms so as to prevent any more such deaths... only for the fish farm, the safe way of making their living that everyone's expectations were pinned on, to be utterly ruined by the red tide.
- Beneath The Snow. Toki is a young man afflicted with a mushi that drops his body temperature and causes it to perpetually snow around him. Unfortunately, he isn't making any effort to take care of himself because he's deeply grieving the sudden and tragic death of his little sister, who fell into the town's frozen lake and died in his arms. Partway through the episode he nearly dies due to walking out onto that same lake and falling through the ice; he only survives because of the mushi snowfall. The episode ends on a hopeful note, but not before Toki has lost several fingers and toes to frostbite... and of course, nothing can bring back his little sister.
- The ending of Azure Waters. Yuuta became a host to a water mushi while still in his mother's womb, and as he grew he became so intertwined with it that it was impossible to separate them despite Ginko's efforts. Eventually it takes over his body completely, resulting in him literally evaporating in his mother's arms. As it begins to rain, the bereaved woman takes comfort in believing that her son now exists everywhere as a force of nature.
- The story Lightning's End is just bleak. Shino is a mother who feels no affection for her son. She once tied him to a tree outside during a storm, covering her ears so she couldn't hear his screaming and crying. He became infected with a mushi that attracts lightning after this, and now whenever there is a storm he climbs a tree in town to keep the lightning away from anyone else, at risk of his own life. Shino struggles with herself throughout to just feel something but whatever is wrong with her won't budge (that she didn't choose to marry the man that is her husband can only account for so much; it's vaguely implied that her relationship with her own mother may have been troubled). Even after her son nearly dies in the climax of the episode, Shino still can't muster up love or affection for him. Ultimately, the boy leaves the loveless home and goes to live with some relatives, which is something of a silver lining.
- Following The Reveal in Lingering Crimson, we see Mikage racked with guilt over stealing Akane's life by stepping on her shadow to escape the mushi. Her husband Youkichi comforts her and himself by hoping that Akane must have also exchanged places with someone else and gone on with her life somewhere else... but at the end of the episode, some time after Mikage's death, Youkichi encounters Akane's shadow and realizes that she was too kind to ever step on another's shadow and consign them to the same fate, and has instead spent decades stranded alone in the mushi's realm. Begging Akane's forgiveness for marrying the girl who banished her to such a fate, Youkichi chases her retreating shadow - and steps on it. The episode ends with Akane (who hasn't aged a day since she vanished) returning to the village, and Youkichi is presumably never seen again.
- One-Eyed Fish: Yoki, having survived a landslide, simply waits by the corpse of his mother as though silently refusing to believe she's dead. Once night falls, he finally gives up and wanders away alone, following a flock of mushi. It gets worse once you realize that after he escaped from the Tokoyami, Ginko lost all memories of his former self as Yoki. Like Nui, not only is his mother dead, she's utterly forgotten about as though she never existed. Ginko may very well not have any living relatives.
- Nui herself is also pretty sad. Having been a traveling mushishi in the past, she'd make frequent trips back to her home village to visit her friends and loved ones. However, one day, a number of them disappear, leading Nui to look for them in spite of how bleak things looked for their survival- when she realized there was Tokoyami living in the pond near her home, it was already too late, both for herself and her missing loved ones. Having Yoki around both made things worse on her, and made her nostalgic for what she lost.
- The backstory of Tagone, the ink stone maker. She wanted to make an ink stone impressive enough to convince her doubtful fiance and his family that she could continue her father's work. When she was finally able to produce such a stone, her fiance asked to take it to show his family, saying that he would send her a letter once he had their approval. When she does get a letter, it's only to tell her that he'd gotten ill and died, and his family sold the ink stone, believing it was cursed. Her father died shortly after this, and Tagone ceased making ink stones altogether. The woman who directs Ginko to Tagone's house makes a point of mentioning that she lives alone.
- "The Mud Weeds" is an all-around tragedy of impulsiveness. Two brothers, Shigeru and Shinobu, had a loving relationship, but ten years prior to the story Shigeru stopped talking to Shinobu after the former's daughter Yuri died. After years of agonizing over the guilt, Shinobu reveals that he accidentally killed Yuri and took her corpse up the mountain where the Mukurosou consumed her body. Shigeru gets so upset that he killed his brother in a fit of rage, and then threw his corpse down a cliff to Make It Look Like an Accident. When his nephew finds out, he becomes afraid of Shigeru and lets Shigeru die as he's drowning in a river.
Tear Jerker / Mushishi