Sepsis is the most common cause of neonatal mortality and is responsible for 30-50% of total neonatal deaths each year in developing countries. The objective of the study was to determine the diagnostic accuracy of C-reactive protein (CRP) in neonatal sepsis. Fifty nine consecutive patients with risk factors and clinical features suggestive of CRP sepsis were selected as per operational definition and fulfilling the inclusion and exclusion criteria. Detailed physical examination was carried out. Blood sample for culture and CRP was taken from all the patients. Results of blood culture and CRP were noted down in the performa. Statistical analysis was performed by SPSS software version 16. Among selected patients 31/59 (52.5%) were male whereas 28/59 (47.5%) were female. Mean age of all patients was 15.47+7.26 days and mean weight was 2.94+0.63Kg. Temperature instability was present in 79.7%, Tachypnea in 69.5%, Tachycardia in 66.1%, delayed capillary refill in 64.4% and oliguria in 55.9%. Blood cultures were positive in 64.4% and raised CRP was found in 64.5%. Sensitivity, specificity, positive predictive value and negative predictive of raised CRP was found to be 97.3%, 95.2%, 97.3% and 95.2% respectively. In conclusion this study show that C-reactive protein has high sensitivity and specificity for establishing the diagnosis of neonatal sepsis which is comparable to that of blood culture results.