<b><i>Background:</i></b> The aim of this study was to evaluate the association of serum osteocalcin with the metabolic syndrome (MS) in men and premenopausal women. <b><i>Methods:</i></b> 14 middle-aged men and 44 premenopausal women were evaluated. MS was defined according to the International Diabetes Federation criteria. Anthropometric data were collected and serum osteocalcin, serum C-telopeptide (CTX), fasting plasma glucose (FPG) and lipid profile measured. <b><i>Results:</i></b> The mean age was 41.07 ± 8.4 years and did not differ between patients with and without MS. Mean osteocalcin was significantly lower in patients with MS (11.18 ± 4.62 vs. 15.09 ± 5.05, p = 0.003) and decreased significantly with the rise in the number of criteria for diagnosis of MS. There were no significant differences in serum CTX between the two groups. Serum osteocalcin was lower in patients with body mass index (BMI) ≥25 (p = 0.038) and FPG ≥100 mg/dl (p = 0.024), and in hypertensive (p = 0.013) and diabetic patients (p = 0.036), and was inversely associated with BMI (p = 0.024), waist circumference (WC) (p = 0.024), FPG (p = 0.007) and systolic blood pressure (SBP) (p = 0.037). <b><i>Conclusion:</i></b> This study showed that lower serum osteocalcin is associated with the presence of MS and that osteocalcin is inversely associated with BMI, WC, FPG and SBP, suggesting that osteocalcin plays a part in the development of MS.