Female sexual dysfunction is a multi-causal and multidimensional problem combining sexual, physiological, physical, psychological, and interpersonal determinants. Loss of libido or loss of sexual desire, as a symptom of one of the primary sexual dysfunctions described in females, is highly prevalent in the general female population. Research on the psychological aspect associated with loss of libido among Hispanic female populations is limited. The objective of this study was to determine how the loss of libido is affected by signs and symptoms of depression, once potential confounders are controlled. Nine-hundred and nineteen Puerto Rican women ages 40 to 59 years living in Puerto Rico participated in health-fairs conducted in twenty-two municipalities between May 2000 and November 2001. Contingency tables and chi-square statistics were used to evaluate the bivariate associations of loss of libido with demographic and lifestyle characteristics, symptom experience and obstetric and gynecologic histories. A logistic regression model was used to estimate the magnitude of the association between loss of libido and signs and symptoms of depression, after controlling for confounders. The overall prevalence of loss of libido in this population was 40.8%. Loss of libido was significantly associated with depressive symptoms (p < 0.05) after adjusting for age, educational attainment, employment status, physical activity, menopausal status/ hormone therapy use and genitourinary symptoms. Women reporting 1-2 depressive symptoms were 67% (95% CI = 1.08-2.60) more likely than women reporting no symptomatology to report loss of libido. The odds of loss of libido increased as the number of depressive symptoms increased [(3-4 symptoms: POR = 3.67, 95% CI = 2.16-5.56); (5-6 symptoms: POR = 5.52, 95% CI = 3.16-9.66)]. Consistent with previous studies, signs and symptoms of depression were significantly associated with loss of libido. Future longitudinal studies should further elucidate the temporal sequence between depression and sexual dysfunctions in this population.