Abstract Background: Obstructive sleep apnea (OSA) is a common condition, but there is a lack of evidence from Saudi Arabia regarding its impact on the academic performance of medical students. Objectives: To determine the prevalence and associated factors of OSA among medical students at a Saudi Arabian university and its impact on academic performance. Methods: This cross-sectional study was conducted between October and December 2021 and selected first- to fifth-year medical students at King Saudi University, Riyadh, using a disproportionate stratified random sampling according to gender and academic year. The questionnaire comprised two sections: the first elicited sociodemographic information, self-reported GPA, and presence of chronic diseases, while the second included the English and Arabic versions of the Berlin Questionnaire. Results: A total of 621 responses were received, of which 61.8% were male and the mean age was 21.1 (±1.7) years. The prevalence of high-risk OSA was 14.5%. There was a significant association between being at a high risk of OSA and male gender (P < 0.001). In the multiple logistic regression model, male gender (odds ratio [OR] = 1.69, 95% CI: 1.01–3.9; P = 0.047) and overweight/obesity (OR = 2.59, 95% CI: 1.92–3.5; P = 0.001) were significant predictors of OSA. OSA was not a significant predictor of academic performance (OR: 0.7, 95% CI: 0.48–1.03; P = 0.07). Conclusion: This study found that among first- to fifth-year medical students at a Saudi Arabian university, male gender and obesity were significant predictors of obstructive sleep apnea. On the other hand, obstructive sleep apnea was not a significant predictor of academic performance.