The Fibromyalgia syndrome (FMS) is characterized by widespread pain and diffuse tenderness in specified locations. The literature clearly points out that FMS is more prevalent in females rather than males, and among patients with major depression disorder (MDD). The aim of the current study was to obtain a better conception of the linkage existing between depression, gender and FMS. Forty-two male patients and 42 age-matched females, as well as age-matched male and female healthy controls were evaluated for coexisting FMS using the American College of Rheumatology (ACR) classification criteria. Each patient completed a questionnaire characterizing the quality of their sleep, a Sheehan disability scale (SDS) and SF-36 scale to measure the quality of life. The degree of depression of each patient was scored using Hamilton depression rating scales (HDRS) and Global assessment was done using the Clinical Global Impression-Severity (CGI-S). Disease parameters were worse for men as compared to women; CGI-S: 5.4 +/- 1 (mean +/- standard deviation), versus 4.0 +/- 1 (t = 6.634, P < 0.001), HDRS: 23.9 +/- 6 versus 20.8 +/- 6 (t = 2.304, P = 0.024), respectively. Yet, FMS was more prevalent among depressed females; 26% versus 2%, (chi2(3) = 9.722, P = 0.002) and so were the average number of tender points (TP) (6.1 +/- 5 versus 2.2 +/- 3, t = 4.399, P < 0.001). The SF-36, SDS and sleep quality scores were similar between males and females. A one-way analysis of variance with gender and disease (depressed vs. non-depressed) revealed that both gender and disease were found to be significant contributing factors for the number of TP (F = 21.131, P < 0.0001; F = 65.232, P < 0.0001, respectively). A one-way analysis of covariance for TP with CGI-S and HDRS as covariates revealed that gender was a significant factor regardless of depression severity (F = 30.028, P < 0.001). CGI-S and Hamilton scores correlated with TP count in females (r = 0.396, P = 0.009, r = 0.531, P < 0.001) but not in males. Female gender is a risk factor for FMS in depressed population. Depression is associated with FMS among women but not among men. Among females, depression severity is significantly correlated to FMS severity. FMS is correlated to sleep quality and to quality of life among depressed patients.