The premise of the series in general is a mix of both this and Nightmare Fuel. A teacher and a handful of high school students find themselves the only survivors of a zombie apocalypse at their high school, with any friends and family all probably dead. Yuki in particular suffers a mental breakdown that's caused her to become delusional and believe that everything is mostly the same as it's always been, while Kurumi has PTSD from having to kill her zombified Senpai. Worse of all, the teacher Megumi is revealed to have died before the girls even met Miki, and the one we've seen this entire time outside of flashbacks was just another part of Yuki's delusions.
The way the first episode subtly builds on the reveal in the climax before going ahead and slapping you hard in the face. Especially with the way the music eventually goes to a sad music box version of the already incredibly bittersweet ending theme.
In the mall, Kurumi makes Rii pinky promise to kill her if she gets infected because she wants to protect the people she loves. It's sad on its own, as it's a girl asking one of her friends to kill her, but in hindsight, it's even worse because Rii can't bring herself to do it after Kurumi gets infected.
Miki getting out of the mall and being told that the others haven't seen a girl around her age. It's essentially a confirmation of her suspicion that the reason Kei didn't come back was because she was turned.
Kurumi screaming in pain while Rii realises that she can't bring herself to kill her friend, even if it's to stop her from turning and killing her.
Miki's message to Kei on the board about how she survived and it was all worthwhile would be sad anyway, but it's even worse because it's shown after they leave the school, and right after Miki sees a zombified Kei stumbling towards the school.
All the scenes involving Megu-nee in it, especially during the finale.
A flashback reveals that Taroumaru originally belonged to a sweet old lady who Miki and Kei met at the mall on the day the Zombie Apocalypse began. Later in the episode, it's revealed that the old lady became a zombie.
This line: Bye-bye, Megu-nee...
The graduation scene at the end of the anime is both this and Heartwarming as the girls finally leave the school, the one place they used as refuge along with the many memories they made in it together, after everything went to hell. Megu-nee's appearance at the end to bid them goodbye would likely make you shed more than a few tears in this scene.
Many ended up full-on sobbing during the scene in episode 2 of Megu-nee protecting Yuki, and comforting her while the zombie shambled past. It got even worse with the revelation about Megu-nee being imaginary, because instead of her older sister figure petting her hair and whispering about how she was safe and loved while they hid, it turns out the scene was really a terrified Yuki curled up alone behind a bookshelf, desperately trying to block it all out. Ouch.
Miki's life after Kei left. She tries to do things like schoolwork or reading to make her life seem more active than it really is, but it's still noticeable she is isolated in a room with zombies surrounding her. Her mini breakdown only makes it more sad.
Megu-nee's death and the chapter centered around her.
Rii is the mature-seeming Cool Big Sis of the group. She seems so calm and above everything, so her Sanity Slippage is all the more tragic. It gets even worse with the implications that her sister is probably dead or worse.
Yuki finds a Precious Puppy one day; however, Megu-nee doesn't allow it around due to it being bit. The puppy came back to them, due to zombies returning to places they remember, and it's heavily implied Kurumi had to kill it.
It can also serve as a meta Tearjerker for anyone who saw the anime before reading the manga. As if having watched Taromaru die in the anime was bad enough, here we have to see it again in the manga, except he doesn't get the peaceful demise he had in the anime and also never gets to bond with any of the girls.
Looks like Kurumi's number is up.
Not quite. Kurumi seems to be okay at the moment. However, Chapter 46 is still sad due to Kurumi having to kill a Melee Fight Crew member by attracting a horde of zombies right to him, in order to keep him from killing her and potentially harming her friends. She's clearly shaken up and horrified by what she just did, and she walks away from the university buildings. Whether this is because of her guilt, wanting to avoid the chance of her turning while in close proximity of her friends, or if she just needs time to think about what just happened is currently unknown, but things still aren't looking too good for her.
When Shino finds out that Kougami was infected not by Takahito or any other particular person, but by the possibility of the Virus being airborne, she slumps against a tree and sadly remarks about how she "can't do anything for Kougami now". It's small compared to other examples in the series, but seeing the MFC's most sympathetic member giving up like that due to not being able to avenge her dead boyfriend and being depressed is pretty heartbreaking nonetheless.
Watching the progression of Kurumi's infection after they leave the college. It's heartbreaking seeing the strongest fighter of the group so powerless.
In Chapter 76, Yuuri remembers that Ruu has been dead for a while, and was killed by a car trying to get her hat back after it was blown by the wind to the middle of the street.
In the final chapter, it turns out that the person who received Yuki's call was shot while trying to broadcast the call on the intercom for the remainder of Randall employees to hear. She managed to convince the splintered organization to stop the bombs and rescue the School-Live club by letting the Randall employees hear Yuki's plea for help, but this faceless woman will never know that her final act saved the world and contributed to finding the cure for the zombie plague.