Introduction Medical students should act as a model for the community in terms of compliance with preventive practices toward COVID-19. The aim of this study was to assess adherence to preventive behaviors related to COVID-19 among medical students and to identify its associated factors. Population and methods We conducted a cross-sectional survey in October 2020 in the faculty of medicine of Monastir. We included a representative sample of medical students during registration days for the 2020–2021 academic year. The data were collected through a self-administered anonymous questionnaire. Eleven items related to preventive practices against COVID-19 were assessed (respiratory hygiene practices (Six Item), hand hygiene practices (Three Items) and social distancing (two items)). Items were evaluated using a Likert scale of five points (from 0: (Never) to 4: (Always)). The score obtained from the sum of these items allowed to classify students into two categories: “Good compliance” if the score was ≥ 80% and “Poor compliance” if the score was less than 80%. Scores were compared according to the study population characteristics. Multivariate analysis was used to identify associated factors with good practices. The threshold of statistical significance was set at p < 0.05. Results We included 678 medical students. The average age was 21.76 (SD = 1.89 years) with a sex ratio of 0.40. The protection measures most respected by the participants were related to the respiratory hygiene: correct coverage of the nose and mouth with the mask (80%), wearing masks regardless of the presence of symptoms (73.3%) and coverage of the mouth during coughing or sneezing (76.6%). Adherence to hand hygiene measures ranged from 51.4% to 66.3%. The least respected measures were related to social distancing: distancing of at least one meter from others (31.2%) and avoiding crowded places (42.5%). An overall score ≥ 80% was obtained among 61.5% of students. Referring to multivariate analysis, variables that positively affected the overall score of preventive measures related to COVID-19 were the female sex and living alone, with Beta coefficients of 3.82 and 1.37 respectively. The perceived level of stress, E-cigarette and Chicha consumption negatively affected the score with Beta coefficients of (-0.13), (-5.11) and (-2.33) respectively. Conclusion The level of adherence to good practice among medical students was overall moderate. Awareness programs would be needed in this population, especially for men and those who smoke and vape.