A 7-year-old cat was presented for a 3-day history of behavioral changes (excessive vocalization, facial territorial marking, inappropriate urination) followed by salivation and focal seizures. At examination, the cat was agitated and pyrexic. It was also hypersalivating and exhibited anisocoria. Treatment with cooling, IV fluids, and anticonvulsants was initiated, but the cat continued to deteriorate. MRI findings were compatible with hippocampal necrosis. Over the next day, the cat began to show improvement; however, it then experienced an episode of vomiting and aspiration of ingesta followed by cyanosis and cardiorespiratory arrest. Initial resuscitation was successful, but the owner declined continued care, and the cat died. Necropsy was grossly unremarkable except for pallor of the hepatic tissues. Histologic changes in the brain showed subacute degenerative encephalopathy involving the hippocampus. The cause of this disease in cats remains unknown.