Procalcitonin (PCT), a prohormone of calcitonin has been described as a specific biomarker of sepsis. Objectives: To compare the predictive value of PCT, C reactive protein (CRP) and white blood cell count (WBC) for the diagnosis of late onset sepsis (LOS) in very low birth weight (VLBW) neonates. Methods: We prospectively determined the serum concentration of PCT, CRP and WBC in 53 VLBW newborns with clinical suspicion of LOS. 25 had confirmed sepsis with positive blood culture; 28 had clinical sepsis (negative blood cultures) Results: PCT levels were significantly higher in the infected group (3.0 ng/ml) compared to the non infected group (0.4 ng/ml) (p < 0.05). PCT had the highest area under the ROC curve 0.83 (95% CI 0.70-0.92) p = 0.001 compared to CRP 0.51 (95%CI 0.37-0.65) and WBC 0.53 (95%CI 0.38-0.66) for the diagnosis of LOS.The best PCT cut off value was 0.9 ng/ml. The sensitivity, specificity and negative predictive value were 88%, 72% and 87%, respectively. Conclusions: The determination of PCT could be more useful than CRP and WBC in the diagnosis of LOS in VLBW newborns.