One Health collaboration is more effective than single-sector actions at mitigating SARS-CoV-2 in deer.

One Health aims to achieve optimal health outcomes for people, animals, plants, and shared environments. We describe a multisector effort to understand and mitigate SARS-CoV-2 transmission risk to humans via the spread among and between captive and wild white-tailed deer. We first framed a One Health problem with three governance sectors that manage captive deer, wild deer populations, and public health. The problem framing included identifying fundamental objectives, causal chains for transmission, and management actions. We then developed a dynamic model that linked deer herds and simulated SARS-CoV-2. Next, we evaluated management alternatives for their ability to reduce SARS-CoV-2 spread in white-tailed deer. We found that single-sector alternatives reduced transmission, but that the best-performing alternative required collaborative actions among wildlife management, agricultural management, and public health agencies. Here, we show quantitative support that One Health actions outperform single-sector responses, but may depend on coordination to track changes in this evolving system.