This case report describes a 40-year-old captive male hippopotamus exhibiting systemic clinical signs, including anorexia and coughing, prior to death. Despite comprehensive medical treatments, the animal died due to age-related immunodepression, which led to severe pneumonia. Necropsy and subsequent histopathological examination revealed severe acute diffuse seropurulent bronchopneumonia, right ventricular hypertrophy, hepatic congestion, and glomerulonephritis. These findings highlight the vulnerability of geriatric large animals to systemic infections and emphasize the need for improved pathological understanding and the development of evidence-based treatment protocols for these less-studied species like the hippopotamus. To enhance disease management and veterinary care for aging zoo animals, future research should prioritize gut microbiome analysis and antimicrobial resistance profiling.