Central fat distribution is significantly associated with an increased cortisol levels. We hypothesized that men with metabolic syndrome have a higher serum cortisol levels compared to women. The purpose of this study was to compare serum cortisol levels, and its correlation with serum leptin levels, between men and women with and without metabolic syndrome. A cross sectional study was performed with 120 untreated patients with metabolic syndrome and 165 healthy volunteers as controls. Serum lipid profile, fasting blood sugar, insulin, cortisol and leptin levels were measured for both groups. Men with metabolic syndrome had a higher serum cortisol levels, while serum leptin levels were significantly higher in women. The higher serum cortisol level in men with metabolic syndrome was significant after multiple adjustments for age, BMI and waist circumference (17.74±5.1 vs 14.07±4.3; p < 0.05) using general linear model; however, these difference were no longer significant when the waist-to-hip ratio was added as one of the adjustment factors (16.7±1.2 vs. 14.9±0.5; p < 0.2). Serum cortisol levels was significantly correlated with serum leptin (r=0.33, p < 0.05), cholesterol (r=0.35, p < 0.05), triglyceride (r=0.25, p < 0.05), waist circumference (r=0.41, p < 0.01) and waist-to-hip ratio (r=0.32, p < 0.01) in women with metabolic syndrome, after controlling for age and BMI. Serum cortisol levels are significantly higher in men with metabolic syndrome. This effect is independent of waist circumference.