If you [[UnsympatheticComedyProtagonist ever have any sympathy for any characters]], there are some moments:
* The Depressing Comic Week ones, when they don't [[CrossesTheLineTwice cross the line back into being funny]] ([[BlackComedy in a horrible and twisted way]]).
** [[http://www.explosm.net/comics/1779/ This one in particular.]]
** Or [[http://www.explosm.net/comics/1777/ this one.]]
** Or [[http://www.explosm.net/comics/2016/ this one]]. Bordering on NightmareFuel.
** Or [[http://www.explosm.net/comics/2015/ this one]].
** If you spend a lot of time reading webcomics, [[http://www.explosm.net/comics/1778/ this one]] is particularly wrenching.
** [[MercyKill especially]] [[http://www.explosm.net/comics/2383/ this one]].
** So, it's daddy's first day as a [[http://www.explosm.net/comics/2998/ policeman]]...
** [[http://www.explosm.net/comics/1244/ This one]], especially the fourth panel.
** [[http://explosm.net/comics/4000 There's nothing worse than too late]].
** [[http://explosm.net/comics/3996/ A kid confronts his deceased father]].
** They've even made a book of these.
* Also, the latter part of Waiting for the Bus, in a weird way.
** The saddest bit is the 50 mph Man [[spoiler: loses the Indy 500]] and soon becomes [[spoiler: a total wreck, with alcohol abuse and smashing all his trophies. Eventually he robs a liquor store, ends up in jail and his wife is forced to divorce him. He soon becomes an old man sitting in the former stadium dedicated to him. Then one day, in a rainy night, he starts running again...[[DownerEnding only to commit suicide by smashing into a wall.]] Soon, the stadium becomes a memorial park. The Bus Driver stops and sees the sign...weeps...[[MoodWhiplash and then the]] [[BrickJoke bus explodes.]] What a DownerEnding.]]
* The Barbershop Quartet [[http://www.youtube.com/watch?v=BPY6lAX9RvM fail to save a man.]]
* The short [[https://www.youtube.com/watch?v=5T03fGBnOjo Missing Daughter]] goes from one Tear Jerker at the beginning to a completely different one halfway through.
* [[http://www.youtube.com/watch?v=Vw8xjDgxzK0 Sad Larry,]] [[http://www.youtube.com/watch?v=RQ-w61_mzyA Sad, Sad Larry,]] and [[http://www.youtube.com/watch?v=iXI1yHP6urk It's A Sad Christmas, Larry]].
* [[http://explosm.net/comics/3752/ These comics are like a prison...]]
* [[https://www.youtube.com/watch?v=N_708QY7Obk The Depressing Episode]]. They are not kidding.
** A man is asking another unseen person whether or not they are alone in the universe. The camera pans out to show that he is talking to a grave.
** The opening of the show starts after with a bird flying around the title [[MoodWhiplash before crashing into the window as the man opens his door as the music becomes more somber]]. The man bends over to the bird before we are treated to a flashback of he and his mother find a dead bird lying on the ground when he was a child. As they comfort each other, he hears a baby bird chirping from a nearby nest, and they adopt it as a pet, whom he raises. [[spoiler:One day as he returns home, he sees an ambulance outside his home and, in the hospital, he is told that his mother had passed away. At her grave, the now adult bird flies off. We are then returned to the modern day, and the man now buries the dead bird next to his mother's grave.]]
** A tree has the words "Jimmy+Anna" with a heart shape carved around it. A man stumbles from behind the tree with a pocket knife and scratches the second name out. [[spoiler:He then begins to cry over it as another shot reveals that Anna was killed when their car collided into the tree.]]
*** [[spoiler:Later in the episode, we go back into this skit with a memorial placed under the carved names. Jimmy walks over to it with a banquet of flowers that he places down next to a picture of Anna. He looks at the picture and smiles. He then crosses his own name out and [[DrivenToSuicide throws a noose over a branch...]]]]
** A man returns home from a trip and thinks that a line of food is for a surprise party. [[spoiler:His mother then gives him the bad news is for a funeral, as his father had committed suicide while he was away. Horrified, he looks over and sees his family grieving over a coffin. His mother then hands him a note saying that it was left for him, reading "Surprise - Dad".]]
** A man and a woman are crossing the street, when the man notices that a car was coming right at her. He runs over and pushes her out of the way quickly [[spoiler:and the car stops in front of him. The driver gets out concerned when the man looks over to see his girlfriend was lying still on the ground. He cradles her and silently yells to a group of onlookers. The next scene gives us a shot of pictures and awards she had won before the reveal that she is now in a vegetative state connected to a breathing tube, with the man brushing her hair for her glumly in front of the mirror.]]
** An elderly woman is trying to eat peas in a nursing home, by her shaking hands won't allow her to pick them up long enough to eat them.
** A man has cancer, much to the dismay of both he and his newly pregnant girlfriend. The shots alternate between check-ups with his doctor and picking out a coffin (which depresses their moods, and with him looking worse in each shot) with check-ups on their baby in utero, picking out names among other things. At one point, the man is hospitalized and the women gives birth. [[spoiler:The baby doesn't live too long, as the father holds its arm as it ultimately flat-lines.]]
*** Oddly enough, this is the only sketch with any sort of joke: [[spoiler: his weirdly small face. One might even laugh at the beginning with the whole "if your hand is bigger than your face" routine, given the absurdity.]] The rest, however, is pure sadness.