Objective: This study sought to investigate the rule of gender in the relation between sexual desire and quality of life in Measure Depression Disorder. Materials & Methods: In this cross-sectional study, 134 subjects (67 male, 67 female) with Measure Depression Disorder were selected through a randomized sampling method from psychology and psychiatry out pationt centers in Tehran. Data for sexual desire were obtained by a single item measure of Beck Depression Inventory-2 and f 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 with respect to 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-being (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 extent 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.