Protected and conserved areas (PCAs) are affected by disease risks and impacts in wide-ranging ways, as demonstrated by recent epidemics and the global COVID-19  pandemic. Their potential role in disease prevention, detection, response, and recovery is significant, both to reduce spillover risks and to effectively prepare for disease events. This report provides an orientation for PCA managers on relevant sources of risk, with actions that can be taken to build up systems to manage disease threats across the variety of PCA contexts. A key message is that protected areas can – and should – play a vital role in One Health approaches to reduce disease risk and improve human, animal, and environmental health outcomes.