Background: The appropriateness of using serum levels of procalcotonin (PCT) for early diagnosis of newborn sepsis is still controversial. Therefore, the objective of the present study was to compare the usefulness of PCT with those of serum levels of C-reactive protein (CRP) and white blood cell (WBC) counts in the diagnosis and response to treatment of neonatal sepsis. Methods: A total of 47 neonates (1-30 days old) were assigned to two control (n=22) and sepsis (n=25) groups. Blood samples were obtained at the outset and after 7 days of treatment for blood culture, measurement of serum levels of PCT and CRP as well as WBC counts. Data were analyzed using within and between group comparisons. Results: Serum levels of PCT were significantly higher in sepsis group (14.1±18.7 ng/ml) than that in the control group (0.38±0.43 ng/ml). In addition, after 7 days of treatment neonates who had achieved clinical recovery had a significantly lower serum PCT levels (0.26±0.37 ng/ml) than that of the same group at the beginning of the study. At a cut-off value of ≥ 0.8 ng/ml, the sensitivity, specificity, positive predictive value of, and negative predictive value of PCT were 84%, 86%, 86% and 84%, respectively. Conclusion: The findings of the present study suggest that serum levels of PCT might be a more reliable marker of infection than serum levels of CRP, or WBC counts in the early diagnosis and responses to antibiotic therapy of neonatal sepsis.