Here we described brain lesion in young captive lions after exhibiting ataxia. The histopathological analyses of the brain showed typical encephalitis with glial cell proliferation, neuronal atrophy and necrosis, and encephalomalacia. We used a variety of identification methods, including next-generation sequencing, polymerase chain reaction (PCR), virus isolation, immunofluorescence staining (IFA), and electron microscopy. Combined with clinical manifestations of the infected cub, it determined that the dead cub have resulted from an FPV embryonic infection. Through sequence analysis, it was found that the infected virus may be a recombinant virus between FPV and CPV. this study not only provides new gene sequences for the global study of FPV-infected lions but also helps to further study the incidence and genetic diversity of FPV.