Medical students face daily challenges such as large workload, time commitment and clinical environment pressure leading to a higher risk of psychological distress. The aim of our study was to assess the relationship between personality traits and depression, anxiety, and stress among Lebanese medical students and to evaluate the mediating role of emotional intelligence (EI) in this association. This cross-sectional study was conducted between June and December of 2019. Participants were from seven medical schools in Lebanon. Higher extraversion (B = -0.11), higher neuroticism (B = -0.28) and higher emotional intelligence (B = -0.03) were significantly associated with lower depression. Higher neuroticism (B = -0.29) and higher emotional intelligence (B = -0.03) were significantly associated with lower anxiety. Higher openness to experience (B = 0.07) and higher agreeableness (B = 0.08) were significantly associated with higher stress, whereas higher neuroticism (B = -0.05) was associated with lower stress. EI mediated the association between extraversion and depression and openness to experience and depression. EI mediated the association between extraversion and anxiety and openness to experience and anxiety. The results of this study were different from those previously cited in the literature. This could be secondary to the mediating role of emotional intelligence. This study consequently opens up the possibility of new studies highlighting the role of emotional intelligence in the possible preservation of medical students' mental health.