This show may be a Denser and Wackier version of The Powerpuff Girls, but it is sure to have at least a few sad moments here and there.
- Anytime Bubbles cries.
- Whenever Blossom cries is slightly sad. Whenever her bow droops due to sadness is is a bit poignant too.
- The fact that Donny doesn't have a father is sad enough on its own, although his mother has a "boyfriend", that may or may not be his biological father.
- "Princess Buttercup"
- Bubbles and Blossom feeling abandoned by Buttercup after she hangs out with the Derby-Tantes more than them.
Bubbles: I miss Buttercup...
- It's hard not to feel at least a little sorry for Buttercup after she figures out that the Derby-Tantes were only hanging out with her because Princess paid them to.
- "Bye Bye Bellum" is not only depressing to longtime fans of the original series for having Ms. Bellum Put on a Bus, but it's also hard not to feel sorry for the Mayor when he's shown to break down over realizing how dependent he's been on Ms. Bellum.
- Bubbles crying over Buttercup's Disney Death in "Little Octi Lost", saying that if she had forgiven her, Buttercup wouldn't have gotten caught in the garbage crusher trying to save Octi.
- In "Arachno-Romance" Sapna Nehru breaks up with the Professor to protect him from her Spider Transformations. While the Professor seemed to get over it, the episode ends with him trying to find a cure for her.
- Bubbles saying goodbye to Cheepy in "Cheep Thrills".
- "Power-Up Puff" is one big Blossom torture porn.
- The scene where Buttercup and Bubbles showing off their aura powers to other kids. Another kid asks Blossom if she has aura powers too, but before Blossom can answer, Buttercup says this:
Buttercup: So what if she doesn't have her new powers yet! And might never get them! Never get them! Never get them! [Each time she says "Never get them", the camera zooms closer in on Blossom's sad face]
Blossom:[Feelings hurt] I gotta go. I'll see you guys at home.
[Buttercup looks worriedly towards Bubbles, looking as if she regrets what she said]
- Right after this happens, Blossom flies down the street in the rain while sad music plays, and sees things that remind her of her mediocrity, and finally breaks down when she looks in a mirror and it breaks. The bow on her head even droops.
Blossom: Geez, I get it! [Sobbing]
- The Professor being heartbroken after he finds out the Girls blabbed about his secrets in "Secret Swapper Of Doom".
- Silico's backstory. His parents were never around, and his only friends were his robots, which were accidentally destroyed by the Girls.
- The same episode, "Viral Spiral", also has a meta example, as it was the last time Chuck Mc Cann voiced the Amoeba Boys before he died on April 9, 2018.
- Blossom running away crying in "Poorbucks" after Princess betrays her.
- Although he is a perpetual jerkass, it is at least a little bit sad to see Manboy getting kicked out of his home, and reduced to a babyfaced coward in Man Up 3: the Good, the Bad, and the Manly.
- The ending song in Home Sweet Homesick.
- Tara Strong not even being contacted by the network if she wanted to reprise her role as Bubbles or not, going on to say that it felt like a stab in the heart.
- To sweeten the pill, she did wish the best of luck to Kristen Li, the new Bubbles.
- Similarly, Catherine Cavadini and E.G. Daily voiced their disappointment while wishing the new voice actresses well.
- The sheer amount of vitriol triggered by the controversial changes made to the show. Many fans who grew up with the Powerpuff Girls in their childhood were excited to see them return to Cartoon Network after so many years, but instead, the changes left many more people angry, confused, or upset than satisfied. It's gotten so ridiculous that some are even questioning whether or not the show truly deserves it.
- As stated above, the Girls' original voice actresses were disappointed when they weren't even asked if they wanted to reprise their roles. Many fans were saddened, too, and some were angry, beleving the network replaced them on account of their age (even though all three are still active and, as the Dance Pantsed special proved, are still able to do the voices the same way they did in 1998).
- The removal of Ms. Bellum was an unpleasant surprise, considering that she was a prominent role model to the Girls in the original series and a reflection of the show's most important message—that a woman can be as intelligent, capable, and strong as a man. The producers attempted to rationalize her removal by saying she didn't send the right message, and fans didn't believe them, believing that Moral Guardians demanded that she be removed simply because of her busty appearance, character traits be damned.