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Understanding how landscape, host, and pathogen traits contribute to disease exposure requires systematic evaluations of pathogens within and among host species and geographic regions. The relative importance of these attributes is critical for management of wildlife and mitigating domestic animal and human disease, particularly given rapid ecological changes, such as urbanization. We screened >1000 samples from sympatric populations of puma (Puma concolor), bobcat (Lynx rufus), and domestic cat (Felis catus) across urban gradients in six sites, representing three regions, in North America for exposure to a representative suite of bacterial, protozoal, and viral pathogens (Bartonella sp., Toxoplasma gondii, feline herpesvirusâ1, feline panleukopenea virus, feline calicivirus, and feline immunodeficiency virus). We evaluated prevalence within each species, and examined host trait and land cover determinants of exposure; providing an unprecedented analysis of factors relating to potential for infections in domesticated and wild felids. Prevalence differed among host species (highest for puma and lowest for domestic cat) and was greater for indirectly transmitted pathogens. Sex was inconsistently predictive of exposure to directly transmitted pathogens only, and age infrequently predictive of both direct and indirectly transmitted pathogens. Determinants of pathogen exposure were widely divergent between the wild felid species. For puma, suburban land use predicted increased exposure to Bartonella sp. in southern California, and FHVâ1 exposure increased near urban edges in Florida. This may suggest interspecific transmission with domestic cats via flea vectors (California) and direct contact (Florida) around urban boundaries. Bobcats captured near urban areas had increased exposure to T. gondii in Florida, suggesting an urban source of prey. Bobcats captured near urban areas in Colorado and Florida had higher FIV exposure, possibly suggesting increased intraspecific interactions through pileâup of home ranges. Beyond these regional and pathogen specific relationships, proximity to the wildlandâurban interface did not generally increase the probability of disease exposure in wild or domestic felids, emphasizing the importance of local ecological determinants. Indeed, pathogen exposure was often negatively associated with the wildlandâurban interface for all felids. Our analyses suggest crossâspecies pathogen transmission events around this interface may be infrequent, but followed by selfâsustaining propagation within the new host species.