* Ed's reaction to Brandy cutting him off from the team in the episode The Big Game.
** Pretty much any moment that makes Ed into a {{Woobie}} qualifies as this.
* Rip Van Whiskers. Well, Whiskers is revealed to have not touched any poison after all so it all ended out fine, but it's still pretty depressing nonetheless.
* Brandy hurting Mr. Whiskers' feelings in "Believe in the Bunny".
* Brandy's actually quite sad breakdown when she discovers she's not a purebred dog, with her giving up on not just primping but taking care of herself in general.