Sexual and gender minority (SGM) populations are particularly vulnerable to poor COVID-19 outcomes and are more likely to experience stigma and medical mistrust that may impact COVID-19 vaccine acceptance. This study examined the prevalence of COVID testing and diagnosis and assessed COVID-19 vaccine acceptance among a large sample of SGM. Participants were recruited as part of an online cross-sectional study focused on an HIV biomedical prevention technology willingness in the United States at increased risk for HIV sero-conversion. Multivariate linear analysis was conducted to examine COVID-19 vaccine acceptance. The study sample included 1350 predominately gay (61.6%), Black (57.9%), cis-gender (95.7%) males with a mean age of 32.9 years. Medical mistrust and social concern regarding COVID-19 vaccine stigma were significantly associated with decreased COVID-19 vaccine acceptance, and altruism was significantly associated with increased vaccine acceptance. Black participants were significantly less likely to accept a COVID-19 vaccine, and Asian participants were significantly more likely to accept a vaccine, compared to White peers. As the planning of COVID-19 vaccine rollout efforts is conceptualized and designed, these data may inform equitable implementation strategies and prevent worsening health inequities among SGM populations.