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One theoretical model suggests that the pathway from pain to depression is through the disruption of social and relationship function. This study sought to test this hypothesis by considering the mediating effect of sexual functioning on the association between pain intensity and depressive symptoms in sexually active patients with chronic low back pain.This was a cross-sectional study on consecutive patients attending a chronic pain management clinic in Iran. All measures (pain intensity, depressive symptoms, sex-specific sexual function) were obtained by a self-report questionnaire, completed by patients while attending the clinic. Sobel testing, including bias-corrected bootstrapping, was used to produce 95% confidence intervals (95% CI) to test the mediating effect of sexual function.A total of 742 patients (351 men, 391 women) took part in this study. Both the male and female mediation models showed a significant association between pain intensity and depressive symptoms, and both the models were significantly mediated by sexual functioning (P<0.001). Effect size calculations show a medium to large effect on male patients (κ2 0.23; 95% CI, 0.15-0.39) and a medium effect for female patients (κ2 0.16; 95% CI, 0.06-0.28). Both the models accounted for over 50% of the variance in depressive symptoms (model R2).This study has shown that sexual functioning significantly mediates the relationship between pain intensity and depressive symptoms in sexually active patients with chronic low back pain. Clinicians may wish to consider the assessment of sexual functioning within this patient group and align treatments that address sexual dysfunction and general pain management.