Objective: To examine the self-efficacy and role of assertiveness as predictor of mediator on mental health among university students. Methodology: This study had 400 university students (200 males and 200 female) selected through convenient sampling technique with age range 20 to 24 (mean 21.5±3.1). Urdu translated Generalized Self Efficacy scale, Depression, Anxiety and Stress Scale, and Self-Assertiveness Scale were used. Results: Self-efficacy and self-assertiveness were significant negative predictors of mental health (Depression, Anxiety and Stress). Self-efficacy was significant predictor of assertiveness. Results supported the meditational role of assertiveness in the relationship between of self-efficacy and mental health (Depression, anxiety & stress). Conclusion: Self-efficacy and assertiveness are important negative predictors of the indices of depression, anxiety and stress on mental health. Self-efficacy influenced mental health indirectly through assertiveness. Gender predicts significant differences in depression, anxiety, and stress.