Background: Medical students display poorer mental health when compared to equivalent peers. Learning environment, educational debt, hard workload, and sleep disturbance make them more liable for mental disorders as anxiety and depression. Objective: The aim of the current work was to determine prevalence and factors associated with depression, anxiety and stress among medical students. Patients and Methods: A cross-sectional study using a self-administered questionnaire was distributed to students in the six grades at Benha Faculty of Medicine. Students were chosen by stratified random sample technique. The total participants were 597. Results: Out of included students; 88.8%, 82.6% & 82.7% experienced depression, anxiety, and stress respectively. A statistically significant difference between smokers and non-smokers (14.3±4.9&11.5±5.6 respectively) was found regarding depression score. The mean anxiety and stress scores were significantly higher between females (9.78±5.4 & 13.03±4.9 respectively) than males. The third grade had the highest mean of anxiety and stress score (10.1±4.8, p value =0.03 &14.02±3.9, p value =0.000 respectively). There was a statistically significant difference in depression and anxiety scores as regarding Personal income. There were statistically significant associations between student average achievement score, social activity, transportation and mean score of depression, anxiety, stress. Conclusion: It could be concluded that medical students experienced high degrees of depression, anxiety, and stress. Smoking, female gender, personal income, achievement score were significantly associated with mental problems.