Carnivores of Madagascar are at increased risk of extinction due to anthropogenic loss of habitat, hunting, and interactions with introduced carnivores. Interactions between introduced and native animals also present the potential for introduction of pathogens into new geographic areas or host species. Here, we provide serologic data regarding pathogen exposure of domestic and native carnivores from the Betampona Natural Reserve Landscape, a protected area in eastern Madagascar. For the Eupleridae, we found limited evidence of exposure to viruses from domestic animals but greater prevalence for Toxoplasma gondii (39%) and Leptospira interrogans (40%). We also evaluated the associations between the presence of antibodies to selected pathogens and the demographic and spatial variables. We showed that individual characteristics such as sex and species were associated with exposure to T. gondii but not to L. interrogans or canine parvovirus (CPV). Finally, we investigated the spatial structure of pathogen exposure in Betampona and found no evidence of spatial structuring, indicating the absence of hotspots and agent-free refugia for T. gondii, L. interrogans, and CPV in the protected area. Our results may be useful for assessing and monitoring disease risk and for formulating control strategies to minimize the negative impact of exotic species on the endemic carnivores of Madagascar.