Introduction: Chronic kidney disease (CKD) is associated with adverse sequelae of cardiovascular disease, renal failure, and premature death. The key factors that could contribute to the development of cardiovascular disease in patients with CKD include inflammation and vascular calcification. Serum fetuin-A, a alpha(2)-glycoprotein is a systemically acting inhibitor of extraskeletal calcification and is down regulated following inflammation. Purpose: To estimate serum fetuin-A levels in patients with CKD and to analyze its relationship with inflammatory biomarkers and calcium-phosphorus levels. Materials and Methods: A total of 80 patients with CKD and 80 healthy, age and gender matched controls were enrolled in the study. Serum levels of fetuin-A, high-sensitivity C-reactive protein (hsCRP), calcium, phosphorus, albumin, lipid profile, glucose, urea, and creatinine were measured. Results: A significant reduction of serum fetuin-A levels were observed in patients with CKD (mean = 0.4416 +/- 0.17 g/L) when compared to controls (mean = 0.7527 +/- 0.18 g/L; P = 0.001). Serum fetuin-A levels also showed a significant negative correlation with creatinine clearance, hsCRP and calcium-phosphorus product and a significant positive correlation with albumin levels (P < 0.01). Conclusion: In CKD, progressive reduction of serum fetuin-A levels occur along with the gradual decline in renal function. The reduced production and increased consumption of serum fetuin-A in CKD could promote vascular calcification and contribute to the cardiovascular disease. Hence, in patients with CKD, measurement of serum fetuin-A could be a promising biomarker to prognosticate cardiovascular risk.