Governments around the world are increasingly considering vaccine mandates to curb the spread of COVID-19. In May 2022, we surveyed 394 residents of South Dakota to examine predictors of popular attitudes toward a COVID-19 vaccine mandate. We investigated the role of Big Five personality traits, right-wing authoritarianism, and social dominance orientation, as well as partisan self-identification, evangelical identity, and COVID-19 vaccination status. Results showed that Big Five personality traits (openness and emotional stability), right-wing authoritarianism, social dominance orientation, evangelical identity, and partisan self-identification are linked to attitudes toward a COVID-19 vaccine mandate. Our findings underscore the politicization of the COVID-19 pandemic as well as the impact of dispositional factors on attitudes toward mandatory COVID-19 vaccination.