Natsume's Book of Friends has tearjerkers aplenty from the very first episode onwards. The sensitive are advised to watch with a wad of kleenex at the ready. Even people who don't cry often would be advised to keep a few kleenex handy.
- In the first episode, Hishigaki calling for Reiko, all alone and crying.
- The second episode with the death of the "Shrine God" because his last worshipper has just died, and there's no one left to pray for him - and even though Natsume offers, it's no good "because you and I are friends". And then we see the final worshipper finally meeting the God in the afterlife.
- That part in Episode Six where Natsume cries upon seeing the photograph of the bird Youkai girl he'd grown attached to, finally getting to be with the human she had so badly wanted to meet all her life, if only for a few hours before she vanished.
- The Zoku episode with Gen and Sui... Just... watch it. Particularly Sui's utter heartbreak when the villagers smash her statue to pieces in anger because they didn't stop the famine, even though it wasn't their jurisdiction, and throw the remains off the cliff. This is the beginning of Sui's descent into demonhood as she asks over and over "why?" Also Natsume comforting Gen in the same episode.
- Any moment where Natsume feels less like an outcast and more like he has a place where he actually belongs doubles as both this and a CMOH. Seriously, just, his absolute bewilderment at actually belonging...
- Tama-chan refusing to eat, and Natsume's realization why. Segues into a Moment of Awesome shortly after.
- The kitsune boy in the manga getting his name turned down, and believing he's useless again.
- The firefly spirit saying goodbye to the man she loved, in the manga, and then dying. Of course, the guy used to love her too, and his Anguished Declaration of Love when he could no longer see youkai was equally heartbreaking.
- Natsume and Reiko's life in general. For Reiko, she couldn't trust humans OR youkai and spent the days picking fights to fill the void. It's shown later that while humans called her a freak, because of her strength, even the youkai called her an omen of disaster. At least Natsume eventually found friends among both youkai and humans, but it's implied Reiko never really had that. Although Natsume's life up until that point was harsh as well.
- From the third episode of season one, there was a youkai who took human form so that she could talk to Natsume and comfort him by pretending that she was a human that could see youkai as well. However, once Natsume found out that the woman he thought was like him was actually a youkai, he rejected her because he felt deceived.
- The first episode of the third season:
- Reiko discovering that the old woman she gave her mirror to and was invited to her home was a youkai after all.
- The Kagejawan is an abandoned teacup-turned-Youkai that is harmless to humans and will even attempt to protect its household from misfortune. One takes up residence in the Fujiawaras' house and ends up sacrificing itself to save Natsume.
- The third episode of the third season has an elementary school classmate of Natsume's come and ask for his help in identifying if that girl he's been seeing is a youkai or not. She is, and in the end, she dies. This doubles as a Heartwarming Moment as well because Shibata (the friend) finally believes Natsume's "lies" and thanks him for his help
- Fourth episode of the third season elaborates on Natsume's utterly craptastic childhood, culminating when a prankster tree-spirit plays one trick too many and sends Natsume careening into a complete hysteric breakdown:Natsume : (Shouting inbetween sobs) Go away. Go away! What did I do to deserve this?! Why do I...? You youkai... I hate you all!
- Episode 4 of Natsume Yuujinchou San, when the youkai haunting a tree drops down to give the revisiting Natsume a gentle hug.
- Episode 5 of Natsume Yuujinchou San when the little youkais watching over the sick Shin'ichiro try to cure him by making their own version of a stethoscope and the little youkai with its hair in a bun sorts of sings to him while shaking the end of the "stethoscope" beside Shin'ichiro's head.
- Just in case there were any doubt about Natsume's Woobie-status, we're informed that not only were Natsume's former guardians abusive and neglectful, but even the relatively pleasant ones treated like him like he was nothing but a nuisance. So when the Fujiwaras show up on their own accord and express a genuine wish to take care of him, Natsume promptly breaks into tears of relief.
- Early on in the third series, Natsume witnesses a cute winged Youkai being violently killed by a ravening face. This deeply upsets him, enough that he's still remembering it and being bothered by it episodes later — even after sealing the youkai that did it. It turns out that the winged youkai was deliberately set out as bait for the big one by the Matoba clan, the revelation of which seriously shakes Natsume's faith in humans. Then he meets the woman who was bonded with that winged youkai, who has sworn revenge against the Matoba clan for what they did. She did some serious damage in her rampage, but it's hard not to feel sorry for her when she's doubled over on the ground sobbing for her lost friend.
- Episode 8 of the third season, when the Rock God performs a Heroic Sacrifice to save the Little Fox.
- An attempt to marathon the fourth series ended literally in tears after the fourth episode, with the voice-mimicking youkai and the human woman he wanted so badly to be happy. Especially how after their brief meetings end he goes on a journey to find the place she felt was so much like home and that, upon his return to their shrine she's long gone and he finally learns what her heartfelt last words to him weren't angry or betrayed at all - only grateful.
- In episode 7 of season 4, both Tanuma and Natsume are filled with insecurities and when they finally admit their insecurities, you can just feel and hear the emotions in their voices. This brings them even closer than before and for Natsume is a big step forward in their friendship. This trope teared up.
- The finale of the fourth season, unlike any other arc up to this point in the anime, took three episodes to build up. During climax of Natsume's flashback, Miyuko shouted and screamed at Takashi to get out of her home, and Takashi promptly ran, almost hysterically, to where he thought his old home was, to return to his "real" home, the home he knew is abandoned and empty, with nothing there waiting for him. All the while painfully crying out for his father over and over again. He didn't manage to reach the house that night, and it isn't until many many years later that Takashi came to give the house one last visit before it gets sold, only to break down in tears once more at remembering the short time he had spent with his father.
- Chapter 65, in which an intimidating ayakashi falls for Taki but obviously cannot communicate with her. He wrote a message on her classroom's chalkboard, but asked Natsume to keep it a secret anyway, and refused to say goodbye since to Taki, he essentially does not exist. Those two adorable rat-bunnies only made it ten times more emotional, as Taki kept trying to communicate with the first one and trying to find its friend, despite not being able to see it and not being able to even use her grandfather's circles any more. And after reading the chalkboard message, Natsume just squeezes his eyes shut and curls up over his desk.The chalkboard message: "I'm lost...you saved me...If it could come true, I would love to bring you to play in that beautiful valley...I wish I could see it with you...this feeling...what do humans call it again?"
- Season 6 Episodes 4 & 5 are about Takuma, an exorcist who has lost the ability to see youkai. In attempt to protect him from vengeful youkai, his daughter places seals around their home in an amateurish way, accidentally trapping one of his former shiki inside the house and two of them outside. Natori suspects that the shiki are causing trouble for the house in hopes that Takuma will die early and free them from their contracts, but this is revealed not to be the case. Instead, the shiki outside intend to prove their usefulness by averting the calamity they summon to the house, under the mistaken assumption that they've been locked out of the house as punishment. Meanwhile, the shiki inside chooses to stay for the rest of Takuma's life, despite the fact that he can no longer interact with her.
- The Season 6 OVA "The Stump of the Suzunaru Tree" features the spirit of a dying tree who clings to life because of a half-remembered promise he'd once made to a human. The human had been a little girl who'd had a fight with her friend, and the youkai had promised that he'd put on a show for her (using his power to make the tree leaves ring like bells) if she brought her friend to visit him again. Natsume finds out that the girl had died shortly after in a car accident, but does make contact with her friend, who is now an adult with a child of her own. She visits the remains of the tree, and the youkai makes the trees ring one last time, much to the delight of the child, to whom he is still visible.
- Chapter 88-89 tells us the origins of the book of friends through the first Youkai whose name Reiko had collected. Reiko had befriended a girl named Souko who challenged her to duels each day to learn her name since Reiko had refused to introduce herself. On the day she finally lost a duel (due to a group of small Youkai startling her) she tells Souko her name and quickly told her leave since it was raining and more Youkai were getting near. The next day however, Souko wasn't there. Or the next. Reiko was convinced that she scared her off her only human friend. Soranome, the Youkai telling the story to Natsume, had found Souko waiting for Reiko and futiley attempted to tell her where Reiko was to no avail. He and Souko both waited for Reiko to return until Souko sadly succumbed to her sickness.
