- The loss of Honey, the adopted sibling of the Looney Tunes Fosters.
- Peter of the Ghostbuster Fosters died in John's arms just four days after birth. Thankfully, it all happened off-camera, but you could tell from John's voice and his shadow how devastated he was.
- The Ghostbusters Fosters were a sad story all around. Mama Janine was found abandoned (in the middle of winter), pregnant, and blind in one eye due to an infection (the eye later had to be surgically removed). Egon was born with a minor defect that made him cross-eyed (though some viewers thought that added to his cuteness). And Baby Peter failed to gain weight properly (despite special care and attention) due to burning off more calories than he consumed, and passed away in John's arms after aspirating on his own milk.
- Thankfully, the family received one of the happiest endings in Critter Room history: Janine, Ray and Egon were all adopted by the same family, preventing them from being split up (as families often are). It got even better when an anonymous donor purchased Peter's tags posthumously (with the proceeds going back to the shelter). Happy tears all around.
- Tragically, two of Patience's five kittens died within a day of each other.
- Three of the five Fabulous Fosters and their mother all tested positive for Feline Leukemia (making them ineligible for adoption). Though they found a permanent home in the Leukemia Room at Purrfect Pals Rescue, Neil passed away from complications related to the illness at a few months old.
- The Reindeer Fosters arrived at The Critter Room severely malnourished. While most of the kittens recovered, Cupid — a favorite of the viewers due his distinctive, "goat-like" voice — passed away at the age of two months. John created a tribute video in his honor.
- As an experiment of sorts, John began bringing in some of his own cats, so they could teach kittens how to behave around adult cats that weren't their mom (as John explains it, mama cats will let the kittens get away with murder, whereas other cats won't be nearly as tolerant). One in particular, Kougra, became a fairly regular fixture of each litter, administering the "kitten flattening paw" to nosey kittens, and even taking part in "dinner dates" when John was fostering an adult female cat with no kittens. However, Kougra also had a bit of an history with various illnesses all taking their toll, so his fans feared the worst when John announced (just a few hours after the Olympian Kittens adoption event) that Kougra was at an emergency vet. A few hours later as test results came through, it became clear he would have to be put to sleep. John then posted two pictures of Kougra resting in his hands, describing how he had been purring and falling asleep, and how the vet had then entered to administer the necessary drugs. Grade A tearjerker material for sure.
- And then it got worse, when just two days later, John reported that Sabby, Kougra's half-sister, who had also become a favourite with the viewers (as John used to put it, she's a few fries short of a happy meal, but pulls it off in a very charming way, so you couldn't help loving her), had been put to sleep following a trip to vet, where it was clear she was suffering several issues.
- And to top it off, a little over a week later, John had to put another one of his own cats down following a series of seizures.
Tear Jerker / The Critter Room