Background: Existing literature has not stablished the factors associated with sleep quality, which requires further research in the context of the mental health of future medical professionals. This study aimed to determine the prevalence and factors related to sleep quality in Latin American medical students during the COVID-19 pandemic. Methods: Cross-sectional multicenter analytic study of secondary data analysis in Latin American medical students. The sampling was non-probabilistic snowball sampling. Sleep quality (Pittsburgh questionnaire) and its association with psychosocial-academic variables, depressive symptoms (PHQ-9 questionnaire), anxious symptoms (GAD-7 questionnaire), resilience (abbreviated CD-RISC questionnaire), eating disorder (EAT-26 questionnaire), physical activity (IPAQ questionnaire-short version), tobacco and alcohol consumption (ASSIST questionnaire) and burnout syndrome (Maslash questionnaire) were assessed. Prevalence ratios and 95% confidence intervals were estimated. Results: Of 2019 medical students, the prevalence of poor sleep quality was 62.2% (95%CI: 60.00%-64.28%). In the multiple regression model, factors that were positively associated with poorer sleep quality were female sex (PR: 1.13), moderate risk of smoking (PR: 1.08), the presence of moderate to severe depressive symptoms (PR: 2.19 and PR: 2.14, respectively), as well as moderate and severe anxiety symptoms (PR: 1.21 and PR: 1.22, respectively). On the other hand, factors that were negatively associated with poorer sleep quality were having received training on COVID-19 (PR: 0.95), having a history of COVID-19 (PR: 0.80), and having a high level of resilience (PR: 0.86). Conclusion: It was found that 62.2% of students had poor sleep quality. Factors such as female sex, moderate risk of smoking, and depressive and anxious symptoms were associated with poor sleep quality, while COVID-19 training, history of the disease, and a high level of resilience were linked to better quality. These findings are key for public health, as poor sleep quality affects physical and mental health and academic performance, underscoring the importance of intervening on these factors to improve student well-being.