Sepsis is a major problem in neonates. Clinical criteria alone could not establish the diagnosis of neonatal sepsis. C-reactive protein, an acute phase protein increases in inflammatory disorder and tissue injury. The present study was conducted to evaluate C- reactive protein (CRP) as a screening tool for neonatal sepsis. A prospective study included newborn infants, aged <90 days and diagnosed with sepsis, who were admitted in neonatal intensive care unit at GCS Medical College Hospital and Research Center, Ahmedabad from 1stJanuary 2015 to 15th April 2015. This study included 100 cases in which 50 were culture proven sepsis and 50 normal newborn. Investigation for infection included CBC, Blood culture, and urine culture. As per the present study, sensitivity of serum CRP was found to be 88% and specificity 84% with NPV of 87.5 suggesting its beneficial role in diagnosing sepsis. Serum CRP was positive in 88% of culture proven sepsis and negative in 12% of cases. P-value of the test applied for the statistical significance is <0.0001 which implies that the result is statistically significant for CRP. Results of the current study indicates that despite the continuing emergence of newer markers of sepsis, CRP still plays a central role in the diagnosis of early onset neonatal sepsis.