The clouded leopard (Neofelis nebulosa) is classified as vulnerable on the International Union for the Conservation of Nature Red List of Threatened Species. However, diseases affecting this species across zoo populations are not well documented. The primary objective of this retrospective study was to identify common and significant causes of morbidity and mortality in captive-bred clouded leopards from European, Asian, and Australian institutions. Medical records from 44 zoological parks that held 271 clouded leopards from 1934 to 2017 were reviewed. Major causes of mortality in the dead leopards (n = 141) were respiratory disease (17%), maternal neglect and starvation (12%), generalized infectious disease (10%), digestive disease (10%), and trauma (10%). Six animals lived more than 20 yr and two were older than 22 yr. Diseases were recorded 344 times (average of two per leopard) in 166 living leopards. The body systems most frequently affected by disease in these 166 individuals were, in order of frequency, integumentary (prevalence = 21%), digestive (21%), respiratory (16%), musculoskeletal (12%), and urinary (10%) systems. Neoplasia (7%) was less frequent, followed by cardiovascular (5%), genital (3%), and viral (3%) disorders. Extensive, self-induced alopecia on the tail and dorsum was the most frequently reported dermatological disease, which is proposed to be called the “clouded leopard alopecia syndrome.” The most common neoplasm was pheochromocytoma (1%), followed by squamous cell carcinoma of the paw pads, pleural mesothelioma and multicentric lymphomas (<1% each). Dilated cardiomyopathy (2%) was the most common cardiovascular disease. Bronchopneumonia (7%), enteritis (4%), and nephritis (4%) were the most frequently reported respiratory, digestive, and renal diseases, respectively. Diagnosed disease incidence was significantly higher in Europe. This paper reports the results of a comprehensive study of the causes of morbidity and mortality in European, Asian, and Australian clouded leopard zoo populations.