OBJECTIVE: The aim of this study was to assess sexual function and related factors (menopause-related quality of life and mood included) in mid-aged Spanish women. METHODS: This was a cross-sectional study in which 179 sexually active women (40-65 y old) completed the six-item Female Sexual Function Index (FSFI-6), the Menopause Rating Scale (MRS), the Hospital Anxiety and Depression Scale (HADS), and a sociodemographic questionnaire containing personal and partner data. RESULTS: Median age was 51 years; 55.3% of the women were naturally postmenopausal, 47.5% had increased body mass index, and 6.7% had hypertension. Currently, 4.5% and 19.6% of the women used hormone therapy and psychotropic drugs, respectively. A total of 87.7% had a stable partner; 1.3% of partners abused alcohol and 8.3% had erectile dysfunction. Of the surveyed women, 36.9% displayed total FSFI-6 scores of 19 or less (lower sexual function); 40.2%, mood morbidity (total HADS scores ≥11); and 23.5%, impaired quality of life (severe total MRS scores ≥17). Cronbach α for the FSFI-6 was 0.91. Total FSFI-6 scores positively correlated with female and partner education and inversely with female age and scores on the MRS and the HADS (total and subscale values). Multiple linear regression analysis found that total FSFI-6 scores positively correlated with partner educational level and inversely (worse sexual function) with female age, partner issues (alcohol abuse and erectile dysfunction), and total HADS and urogenital and somatic MRS scores. CONCLUSIONS: In this mid-aged Spanish sample, as assessed with a short and consistent tool, lower sexual function was related to menopausal and mood symptoms and several women and partner factors. Further research using this instrument is warranted.