Translocations have been widely used to restore and conserve bighorn sheep (Ovis canadensis) populations in North America. Some translocations have been successful, but many populations remain small and genetically isolated. Population structure can influence the viability and long-term success of reintroductions. Social ungulates often function as interconnected subpopulations (metapopulations); however, few studies evaluate subpopulation sizes, connectivity, and genetic diversity within metapopulations. To address this gap, we conducted a comprehensive study of a reintroduced Rocky Mountain bighorn sheep (Ovis canadensis canadensis) population in Dinosaur National Monument in Colorado and Utah, USA, between 2006–2020. We analyzed global positioning system (GPS) radio-collar data, genetic samples, and results of health testing to evaluate abundance, distribution, genetic structure and diversity, habitat use, movement and connectivity, and presence of or exposure to respiratory pathogens. We integrated these analyses to evaluate the outcomes of a reintroduction effort that began in 1952, over 70 years ago, and to inform management decisions in Dinosaur National Monument. We also provide a framework for evaluating metapopulation processes, including a non-invasive approach that links genetic structure with Bayesian spatial capture-recapture analyses to estimate subpopulation sizes. Despite models indicating continuous suitable habitat, we found a spatially structured population with at least 4 subpopulations with constrained connectivity. Evidence from step selection and density analyses suggested that movement among subpopulations may be limited by semi-permeable barriers including rivers and human disturbance, which could contribute to maintenance of spatial structure over time. In 2006, antibody to Mycoplasma ovipneumoniae was detected in all geographically and genetically distinct subpopulations. Widespread clinical signs of disease and a confirmed exposure to M. ovipneumoniae in 2019 indicate a long-term disease challenge. Proximity to domestic sheep creates repeated opportunities for introduction of new M. ovipneumoniae strains. We estimated abundance in 2019 at 109 (95% CrI = 87–133), composed of subpopulations ranging from 18–39 animals (95% CrIs from 11–50). Genetic diversity was relatively high compared to other reintroduced and native Rocky Mountain bighorn sheep populations, which is likely a consequence of multiple translocations from different sources. Three of 4 subpopulation centers generally aligned with the locations of original translocation release sites. Persistence in the presence of pathogens may be facilitated by metapopulation structure and moderately high genetic diversity. Conversely, metapopulation structure can also facilitate pathogen persistence. Our approach offers a path to advance understanding of the population ecology of reintroduced bighorn sheep and can inform effective conservation and management of their populations.