- Episode 5 has Mai's flashbacks to her mother, and her realization that choosing to ignore the Orphan bus led to deaths and memory erasures.
- Episode 8, when Akane watches her boyfriend Kazuya get killed and is rendered functionally comatose for a good portion of the series.
- The ending of episode 15, after Alyssa is shot to death and passes away in Miyu's arms, and then Miyu takes her corpse and seals herself in a lake in despair. The choice of ending music for this episode doesn't help at all.
- In Episode 20, when everyone starts fighting each other and poor Takumi becomes the next casualty, evaporating in Mai's arms after Akira's CHILD is struck down (even Mikoto broke down into tears when she realizes it was her fault). And the episode was also very cruel to Mai, who learns that Nao has attacked her younger brother, who said that he didn't need her anymore, regardless of how much she cared about him. After finally catching up to Akira and Takumi, Gennai is slain, killing Takumi. He dies in Mai's arms and she screams at the heavens in a voice that could jerk tears on its own. Her body doesn't even seem to be functioning properly as she turns to face Mikoto, the same girl who lovingly glomped Mai every chance she got, who only slowly realizes what it is that she'd done. Mai on the other hand is so enraged that her face twists up in a horribly pained expression, to the point where she draws blood from biting her lip so hard. As if it wasn't bad enough, when Mikoto finally stops, and stares at Mai, crying her eyes out, Kagutsuchi blasts Mikoto full on, apparently killing her. Mai could do little to stop it. And she walks away like a living doll, her head limply falling from side to side.
- The scene shortly before where Takumi decides he won't go to America for a possibly life-changing but very expensive operation because he knows how much of a burden he is to his sister — unaware that she's listening.
- Episode 23, with a defeated Midori staring into the distance after basically sacrificing the man she adores to preserve what might or might not be a chance for someone else to live. "I'm sorry, Professor, but you would be proud... right?"
- Takumi's apparent death in the manga, particularly his sister Mai's reaction. He gets better... but then things get much worse.
- Episodes 24 and 25, where Yuuichi dies in a way that seems so coldly logical when you see it and still manages to die with a smile on his lips, and where Natsuki and Shizuru kill each other in an inevitable double-KO both saw coming. There is also the part late in the episode where Mai reads all the names of the people who lost their loved ones in the conflict, a list that includes some of her friends. And then Shizuru and Natsuki are added to that list.
- Even if Akane losing Kazuya leaves you too stunned for tears, the following events are utterly heart-wrenching: No one knows what happened, they think Akane and Kazuya just eloped, and the high school comedy continues as normal. Then, when we finally see what happened to Akane after that scene....
- The episode where Nao loses her eye during her battle with Natsuki might also count, but you only realize it afterwards, when it's revealed that she was framed, and Natsuki was tricked by Sister Yukariko into fighting her - putting Nao's loss of an eye and tearful/furious/revenge-swearing exit in a very different light.
- Nao's definitive defeat at the hands of Shizuru is even more tear-jerking. Especially when Nao has an Heroic BSoD, starts crying and screaming for her Missing Mom, who spent several years comatose and was killed when Shizuru killed her CHILD.
- Haruka's death and the flashback to her and Yukino's childhood.
- The final episode jerks tears of the happy variety, as everyone lost is resurrected.
Tear Jerker / Mai-HiME