Objective To determine the association between sexual function and depression in sexually active, mid-aged women while controlling for sociodemographical and clinical factors. Methods Data were analyzed from 335 healthy, sexually active, Peruvian women (4059 years) who simultaneously filled out the Female Sexual Function Index (FSFI), the Menopause Rating Scale (MRS), the Beck Depression Inventory (BDI) and a general questionnaire containing female/partner data. Correlations between the measures of all tools were analyzed. Results The median age of studied women was 49 years; 76.7% had low schooling, 40% were postmenopausal and 15.2% used hormone therapy. Regarding the partner, 11% and 10.5% presented erectile dysfunction and premature ejaculation, respectively. FSFI total scores displayed significant correlations with BDI and MRS scores (total, psychological and urogenital). Multiple linear regression analysis was used to obtain an association model between sexual function and depression, explaining 88% of the variance. In this model, sexual function was inversely associated with depression, yet confounded by MRS urogenital scores. In addition, sexual function was inversely correlated to partner sexual function and to female MRS psychological scorings and positively to premenopausal status. Conclusion In this mid-aged series, sexual function was significantly associated with depression, in addition to hormonal status and partner sexual function. © 2011 International Menopause Society.