Introduction: Stress, anxiety, and depression can be associated with severe harmful consequences to the physical, mental and social well-being of the affected populations. This study was conducted to determine the prevalence of stress, anxiety, and depression among medical students at Tabuk University and to identify the associated risk factors. Methods: Cross-sectional study, self-administered questionnaire distributed among medical students at Tabuk University. Results:The completequestionnaires were received from 241 participants giving a response rate of 62.7%.Prevalence of depression among medical students was 28.6%, anxiety 46.05%, and stress 13.2%. prevalence of depression among basic years was 38%, anxiety 53%, and stress 7.7% while the prevalence is less in clinical years at 27%, 44%, and 5.6% for depression, anxiety and stress respectively. The prevalence of depression was higher among female medical students at 41.1% while the prevalence in males was 21.9%. anxiety is also higher in females 56.6% and 38.1% and males. Stress was 9.5% in female and 2.5% in male medical students. In our study, the factors that affected stress, anxiety, and depression among medical students. Gender, previous history of depression or anxiety, family history of suicidal attempts, and mental illness were determinant factors for stress, depression, and anxiety. Also, stress was significantly affected by academic performance. Students with good, very good, and excellent academic performance tended to have no stress. Conclusions: Our findings in this study suggest that anxiety and depression are prevalent among Tabuk University medical students.The prevalence more in female and basic years medical students. Other risk factors include previous history of mental illnesses, a family history of suicidal attempts, and academic performance.