This commentary discusses the contributions that One Health (OH) principles can make in improving the global response to the COVID-19 pandemic. We highlight four areas where the application of OH has the potential to significantly improve the governance of infectious diseases in general, and of COVID-19 in particular. First, more integrated surveillance infrastructure and monitoring of the occurrence of infectious diseases in both humans and animals can facilitate the detection of new infectious agents sharing similar genotypes across species and the monitoring of the spatio-temporal spread of such infections. This knowledge can guide public and animal health officials in their response measures. Second, application of the OH approach can improve coordination and active collaboration among stakeholders representing apparently incompatible domains. Third, the OH approach highlights the need for an effective institutional landscape, facilitating adequate regulation of hotspots for transmission of infectious agents among animals and humans, such as live animal markets. And finally, OH thinking emphasizes the need for equitable solutions to infectious disease challenges, suggesting that policy response mechanisms and interventions need to be reflective of the disproportionate disease burdens borne by vulnerable and marginalized populations, or by persons providing health care and other essential services to those sick.