This study was undertaken to assess vitamin D status in nonmenopausal women with metabolic syndrome (MeS) and to evaluate its possible role in inflammation and other components of MeS. A case-control study was conducted during late fall and winter 2009-10. A total of 375 women with waist circumference (WC) ≥88 cm were examined to find 100 who met MeS criteria according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel (ATP) III criteria (NCEP/ATP III). Of those without MeS, 100 age- and residence area-matched women were selected as a control group. Anthropometric and laboratory evaluations were performed. Waist-to-hip ratio (WHR), body mass index (BMI), homeostatic model of insulin resistance (HOMA-IR) and body fat mass (FM) were also evaluated. Women with MeS had significantly higher BMI, waist circumference (WC) and FM but lower serum osteocalcin than controls. There was no significant difference in serum 25 hydroxyvitamin D (25[OH]D), intact parathyroid hormone (iPTH) or vitamin D status between the two groups. Serum highly sensitive C-reactive protein (hsCRP) concentration was significantly higher in the MeS group, compared to the controls (3.4 ± 3.3 vs 2.0 ± 1.9 mg/L, P < 0.001). The difference remained significant even after controlling for BMI (P = 0.011), WC (P = 0.014) and FM (P = 0.005). When comparison was made only in those subjects with insulin resistance (HOMA-IR > 2.4), hsCRP was still higher in the MeS group (n = 79) than in the control group (n = 61) (P < 0.001). When data were categorized according to vitamin D status, in the MeS group significantly higher plasma glucose concentrations were observed in subjects with vitamin D deficiency compared to those with insufficiency or sufficiency (104.0 ± 11.7, 83.0 ± 11.3 and 83.2 ± 9.9 mg/dL, respectively, P < 0.001). Interestingly, their WC or WHR did not show any significant difference. In stepwise regression analysis, 25(OH)D was the main predictor of both hsCRP and plasma glucose. Vitamin D status may, at least in part, be a determining factor of systemic inflammation and the related metabolic derangements of MeS.