Objectives: The aim of this 2017 study is to identify the prevalence of depression, anxiety, and stress and their association with Najran university male medical students’ age, monthly income, living status, academic level, daily studying hours outside the university, and the personal problem factor. Also, the authers aim to find out the correlation and its significance if found between depression, anxiety, and stress among the study participants. Methods: This study is cross-sectional and used a mixed approach (quantitative and qualitative) with 49% (i.e. 67 students) response rate. All population was included in the study due to its small size [i.e. (N=136), including all levels of male medical students at Najran University and excluding female medical students and first year-students]. Data was anonymously collected using a hardcopy self-administrated survey (DASS-21-tool). Descriptive and inferential statistics were done using the Statistical Package for the Social Sciences (SPSS) Software. Results: Overall, the prevalence of depression, anxiety, and stress was high. Stress was significantly associated with the living status of the students (P=0.028), while academic level and daily studying hours outside the University were significantly associated with depression with P=0.015 and P=0.023 respectively. However, no significant association was found between anxiety and any variable in our study. Also, there was a positive association between depression and anxiety, between depression and stress and between anxiety and stress scores. Conclusions: With a high prevalence of depression, anxiety, and stress among male medical students is reported, this issue should be considered when planning educational programs for medical students.