To compare the utility of procalcitonin (PCT) vs C-reactive protein (CRP) as indicators of late-onset neonatal sepsis in very low birth weight (VLBW) infants. PCT and CRP levels were measured in VLBW infants with suspected sepsis and controls. Comparisons were made between infected vs noninfected infants. Using cutoff values of 0.5 and 1.0 ng/ml for PCT and 0.8 mg/dl for CRP, sensitivity, specificity, positive and negative predictive values were calculated to evaluate these assays as potential predictors of late-onset sepsis. A total of 67 infants were evaluated. Mean PCT levels were significantly higher in the infected group (5.41 ng/ml) compared to the noninfected group (0.43 ng/ml) (p < 0.001). At a cut off value of 0.5 ng/ml, the sensitivity of PCT was 97%, whereas that of CRP was 73% in predicting late-onset sepsis. At a PCT cutoff of 1.0 ng/ml, sensitivities of PCT and CRP were similar (72% each). PCT (0.5 ng/ml) is more sensitive than CRP in predicting late-onset sepsis in VLBW infants.