The development of vaccines against COVID-19 has given hope to populations. Public acceptability of vaccination is a major driver in containing the disease. However, in marginalized and stigmatized populations, uncertainty and unwillingness may be a challenge. This study aimed to analyze the factors associated with uncertainty and unwillingness to vaccinate against COVID-19 in men who have sex with men (MSM) living in France. The data used came from Rapport au Sexe (ERAS) 2021, a voluntary, cross-sectional, anonymous, self-administered, online survey conducted from 26 February to 11 April 2021. Among the 15,426 respondents included in the analysis, 60.5% were willing to vaccinate (these included persons already vaccinated), 17.5% were not, and 22% were uncertain. Factors independently associated with uncertainty and unwillingness were lower education level, low health literacy level, financial hardship, being under 30 years of age, and living in a rural area. HIV-positive MSM were less likely to report vaccination uncertainty and unwillingness than HIV-negative MSM and those with unknown serostatus. Although more impacted by COVID-19, socioeconomically vulnerable MSM were the sub-group most unwilling to vaccinate. To improve acceptability of COVID-19 vaccination in MSM, policy makers and researchers must increase access to and understanding of medical information by considering the general public's health literacy when developing information sources. Moreover, a dedicated global care approach, which ensures these populations can be reached, is necessary.