A high worldwide SARS-CoV-2 vaccine coverage must be attained to stop the COVID-19 pandemic. In this study, we assessed the level of willingness of Mozambicans to be vaccinated against COVID-19. Data were collected between 11 and 20 March 2021, through a self-administered online survey. Of the 1878 respondents, 30.1% were healthcare workers, 58.3% were aged between 18 and 35 years, 60% were male, and 38.5% were single. Up to 43% had been tested for COVID-19 and 29% had tested positive. Overall vaccine acceptability was 71.4% (86.6% among healthcare workers, 64.8% among other respondents; p < 0.001). Reasons for vaccine hesitancy included: fear of vaccine side effects (29.6%) and the belief that the vaccine is not effective (52%). The acceptability of the SARS-CoV-2 vaccine increased with increasing vaccine efficacy. Using logistic regression, determinants for acceptability of the vaccine were: older age, a past COVID-19 test, a concern of becoming (re)infected by COVID-19, having a chronic disease, and considering vaccination important for personal and community health. In conclusion, vaccine acceptability in Mozambique was relatively high among healthcare workers but significantly lower in the rest of the population. This suggests that there is a need to educate the general population about SARS-CoV-2 vaccination and its importance.