Simple SummaryIn South Africa, thousands of African lions are bred on farms for commercial purposes, such as tourism, trophy hunting, and traditional medicine. Lions on farms often have direct contact with people, such as farm workers and tourists. Such close contact between wild animals and humans creates opportunities for the spread of zoonotic diseases (diseases that can be passed between animals and people). To help understand the health risks associated with lion farms, our study compiled a list of pathogens (bacteria, viruses, parasites, and fungi) known to affect African lions. We reviewed 148 scientific papers and identified a total of 63 pathogens recorded in both wild and captive lions, most of which were parasites (35, 56%), followed by viruses (17, 27%) and bacteria (11, 17%). This included pathogens that can be passed from lions to other animals and to humans. We also found a total of 83 diseases and clinical symptoms associated with these pathogens. Given that pathogens and their associated infectious diseases can cause harm to both animals and public health, we recommend that the lion farming industry in South Africa takes action to prevent and manage potential disease outbreaks. African lions (Panthera leo) are bred in captivity on commercial farms across South Africa and often have close contact with farm staff, tourists, and other industry workers. As transmission of zoonotic diseases occurs through close proximity between wildlife and humans, these commercial captive breeding operations pose a potential risk to thousands of captive lions and to public health. An understanding of pathogens known to affect lions is needed to effectively assess the risk of disease emergence and transmission within the industry. Here, we conduct a systematic search of the academic literature, identifying 148 peer-reviewed studies, to summarize the range of pathogens and parasites known to affect African lions. A total of 63 pathogenic organisms were recorded, belonging to 35 genera across 30 taxonomic families. Over half were parasites (35, 56%), followed by viruses (17, 27%) and bacteria (11, 17%). A number of novel pathogens representing unidentified and undescribed species were also reported. Among the pathogenic inventory are species that can be transmitted from lions to other species, including humans. In addition, 83 clinical symptoms and diseases associated with these pathogens were identified. Given the risks posed by infectious diseases, this research highlights the potential public health risks associated with the captive breeding industry. We recommend that relevant authorities take imminent action to help prevent and manage the risks posed by zoonotic pathogens on lion farms.