Objective: This study sought to investigate the role of gender in sexual desire and quality of life's correlation in Major Depression Disorder.Materials & Methods: In this cross-sectional study, 134 subjects (67 male, 67 female) with Major Depression Disorder were selected through a randomized sampling method from psychology and psychiatry outpatient centers in Tehran. The data for sexual desire were obtained by a single item measure of Beck Depression Inventory-2 and quality of life by Short Form 36 (SF-36) and McGill Quality-of-Life Questionnaire. The bivariate correlations between the quality-of-life sub-domains and sexual desire were analyzed with the Pearson test in the males and females, separately.Results: There was no statistically significant difference between the two genders in terms of sexual desire (P=0.230). The SF-36 showed that sexual desire correlated in both genders with pain (r=-0.456 and P<0.001 for the males; r=-0.308 and P=0.011 for the females). The SF-36 also demonstrated the correlation between sexual desire and physical functioning variables (r=-0.457, P<0.001), role limitation due to physical problems (r=-0.325, P=0.007), role limitation secondary to emotional problems (r=-0.325, P=0.007), fatigue (r=-0.294, P=0.016), emotional well-beinp (r=-0.368, P=0.02), and social functioning (r=-0.483, P<0.001). The McGill inventory questionnaire demonstrated correlations between sexual desire and psychological well-being (r=0.255, P=0.037), existential well-being (r=0.293, P=0.016), and social support (r=0.425, P<0.001) in the men.Conclusion: The more and extensive link between sexual desire and quality of life in Major Depression Disorder showed the more effect of changes in sexual desire due to depression on quality of life in male than female subjects.