State-issued mask mandates were associated with a reduction in COVID-19 hospitalization rates across the United States during the early phase of the pandemic. As new variants of the SARS-CoV-2 cause spikes in COVID-19 cases, reimposing mask mandates in indoor and congested public areas, as part of a layered approach to community mitigation, may reduce the spread of COVID-19 and lessen the burden on our healthcare system.