- Devil In The Sand ends on a pretty bleak Downer Ending: Cash discovers that the murderer he was investigating to be his own adoptive father Gus, who is revealed to be a Gaelic vampire and in league with Skinner Sweet. In a confrontation against the Carpathian vampires (who were targeted by Gus and Sweet), Gus is betrayed by his associate and murdered before his son. Afterwards, Sweet finds Cash's pregnant wife Lily and injects her with his vampire blood just to spite him. She dies giving birth to a extremely disfigured vampire baby, leaving Cash's life completely in tatters.
- Ghost War has some really gut-wrenching moments.
- The opening scene has Henry fighting on World War II and pinned down against enemy fire, writing seemingly his last letter to Pearl.
- When the team of Vassals is captured by Japanese scientists experimenting with vampires, one of their members is infected with the virus and immediately turns into a Japanese Vampire. What makes this heartbreaking is 1) just before said member turns into a monster he tells his mates that it was an honor fighting on their side and 2) one of his friends pleads that they don't leave him like this and give him mercy.
- Calvin reminiscing about his friend's tragic backstory.
- The Vicar pulling a Heroic Sacrifice as soon as he is bitten by a Japanese Vampire. He clings long enough to tells his own backstory to the two surviving members of the team, how he refused to give mercy to his own little son who also was turned, and he ended up biting his arm, forcing Vicar to cut it down so the infection wouldn't spread. This makes his sacrifice even more poignant and to further twist the knife, he turns just seconds before he detonates the grenades.
- Survival of the Fittest shows what happened to poor Gus McCogan. He had been locked in a cage and fed small animals for his father since he was born as an American vampire.
- When Cash is instructed by the Nazis to test a sun-gun in some captured vampires, he doesn't hesitate to fry them when on the spot. Until he is told to fry a Gaelic-Prime vampire, which reminded him of both his father and his son. He can't help but look so broken that he nearly blows their cover.
- Henry's death
- His last letter to Pearl is particularly lachrimal-inducing. Even worse as one of the last things Pearl did was betray him utterly by cheating on him with Skinner in a moment of weakness.
- The Long Road to Hell: A young couple in love are transformed into vampires against their will. They try to stave off their thirst for blood by hunting on people they assume won't be missed, driven by the promise of a cure in Las Vegas. Unfortunately, once they arrive they find out that the rumors are false: it was a trap set by Travis Kidd for the people who were responsible for the couple's vampirism. Saddened by this, the couple decide to get married before allowing Kidd to Mercy Kill them, letting them at least die with a shred of happiness after their ordeal.
Tear Jerker / American Vampire