The Asiatic lion (Panthera leo persica) is an endangered species with a slowly increasing captive and wild population. Several zoos from within the European Association of Zoos and Aquaria Ex Situ Program reported Asiatic lions with neurological signs such as (progressive) ataxia, and stargazing. The aim of this study was to evaluate the frequency (prevalence and incidence) and etiology of these clinical signs within the captive Asiatic lion population. The medical history of 74 Asiatic lions (36 healthy and 38 affected) was retrieved and reviewed for blood tests (biochemical, hematological, and retinol), diagnostic imaging (MRI and CT scans) and postmortem examinations. The data of the affected lions was compared with those of healthy lions. Between 2002 and 2020, the prevalence of ataxia ranged from 0.6% in 2004 to 13.0% in 2020. The incidence of ataxia was variable per year between 2002 and 2020 and ranged between 0 and 40%. Besides ataxia, stiffness and lameness were the most described signs in this study. Blood results showed lower total protein, ALT and creatinine, and higher phosphate in lions with neurological signs. Moreover, neurologically affected lions showed a significant lower blood retinol than the control lions (0.59–0.81 µmol/L). The most important finding in diagnostic imaging and necropsy included caudal fossa hyperostosis and cerebellar herniation. These abnormalities are similar as found in African lions (Panthera leo) with calvarial hyperostosis syndrome associated with vitamin A deficiency. Leucomyelopathy, syringomyelia (in one case combined with cerebellar herniation) and incidental mineralization of the dura mater were also described. A possible congenital/hereditary component should not be excluded.