Hybridisation between wild and domestic species poses a serious challenge to conservation management and can lead to extinction, through genetic introgression. Additionally, during interbreeding, infectious disease transmission can occur. However, the link between hybridisation and disease transmission has historically been neglected. In Scotland, the European wildcat (Felis silvestris) is critically threatened by hybridisation with the domestic cat (Felis catus). Complex introgression has resulted in a ‘hybrid swarm’, a genetic continuum between the wild and domestic species. As a consequence, the wildcat population in Scotland was considered non-viable, without restoration through captive breeding and release. To strategically shape and safeguard these required translocation actions, and on the basis that the hybridised population might act as a bridge for disease transmission between the two species, a One Health approach to the wildcat – domestic cat interface became crucial. A comprehensive health assessment - including wildcats, domestic cats, hybrids and their environment -, combined with genetic research, was the foundation to inform the disease risk analysis and mitigation practices now implemented by the ‘Saving Wildcats’ translocation project. It was concluded that the ‘hybrid swarm’ may now be functioning as a single epidemiological unit: the interactions between wildcats and domestic cats that resulted in the genetic continuum, may also have allowed a more homogenous transmission of infectious agents. This provides a new insight into the epidemiology of hybridised populations. Ultimately, this integrative approach could be applied to inform targeted conservation of other species, where hybridisation and parallel infectious disease transmission are considered potential threats.