Case summary A 2-year-old neutered male domestic shorthair cat presented for a history of several weeks of infrequent urination and hyporexia progressing to anorexia. The cat had been normal prior to being placed on fluoxetine to treat inter-cat aggression, after which it began to display weight loss, hyporexia and abnormal urination habits. The cat had been seen by various veterinary hospitals previously and treated for suspected feline lower urinary tract disease. When the patient still had urinary retention despite perineal urethrostomy surgery, it was presented for ongoing care. Contrast urethrogram showed a mild questionable proximal ureteral narrowing, but other diagnostics were unremarkable. The patient was trialed on various medications, including alpha-antagonists, cholinergics, non-steroidal anti-inflammatory drugs and different analgesics with no improvement, but would reproducibly urinate only following administration of midazolam intravenously. Ultimately, the cat began urinating normally following the discontinuation of fluoxetine. The cat was urinating normally upon discharge, and when it presented for another complaint several months later, its weight, appetite and urination habits were normal.