Introduction: Neonatal sepsis is a major cause of morbidity and mortality in the neonatal period, inspite of extensive use of antimicrobial therapy. Early diagnosis of the newborn with early onset neonatal sepsis (EOS) is difficult because Initial signs of EOS are slight and nonspecific and laboratory tests including the "gold standard" blood culture are not always reliable.Objectives: The aim of this study was to evaluate the accuracy of C-reactive protein measured by a highly sensitive assay in diagnosis of EOS. Study design: Peripheral blood samples were taken from 90 neonates who were categorized into two groups: proven or clinical sepsis (n=60); and healthy controls (n=30). Blood cultures, CBC with differential and qualitative CRP have been evaluated in a prospective manner as a diagnostic aid for neonatal sepsis. Results: CRP using high sensitivity immunoassay at a cut off level 2 mg/L in diagnosis of EOS had sensitivity 66.7%, specificity 100%, positive predictive value 100%, negative predictive value 60% and diagnostic accuracy 77.8%. Conclusion: we confirm that CRP analysis using a highly sensitive immunoassay is likely to improve the diagnostic accuracy of CRP in detection of early onset neonatal sepsis. Only 40 µl of serum is needed, and results available within 15 minutes.