BackgroundLittle is known about public perceptions of antivirals for the treatment of mild-to-moderate COVID-19 in the United States (US). Our objective was to explore adult perceptions toward COVID-19 antivirals with the goal of improving outreach communications about antivirals for COVID-19.MethodsDuring July 2022, potential respondents 18 years and older were randomly sampled from a national opt-in, non-representative, cross-sectional internet panel, with oversampling of African Americans, Hispanics, and adults 65 years and older. Respondents were asked about sociodemographic factors, and knowledge, attitudes, and perceptions regarding COVID-19 antivirals. Results were weighted to represent the US population.ResultsAmong 1,155 respondents, 51% were female, 60% were 18-49 years, 21% were 50-64 years, and 19% were 65 years or older. Compared to those aged 18-49 years and 50-64 years, a greater proportion of adults 65 years and older were knowledgeable about COVID-19 antivirals and would take them if they tested positive or their doctor recommended them. Adults 65 years and over and those reporting immunosuppression or disability had the highest rates of willingness to take antivirals. For all groups, the proportion of people willing to take antivirals increased by >20% if recommended by their doctor. Respondents in the 50-64 and 65+ groups who were sure they would take COVID-19 antivirals were more likely to be fully vaccinated and less likely to be living in isolation.ConclusionGroups that are less likely to have been vaccinated, those living in isolation, and those not sure about whether they would take an antiviral or not may be at risk for not receiving treatment to prevent severe COVID-19 outcomes. However, trust in doctor recommendations may be enough to overcome individual patient concerns about COVID-19 antivirals. Targeted initiatives to educate those at risk for severe COVID-19 outcomes about the effectiveness of antivirals, including those who are unvaccinated given their increased risk of severe disease, may be needed to further lower this population’s risk of severe COVID-19.