Introduction: Neonatal sepsis (NS) is leading cause of mortality and morbidity in neonates specially in developing countries and early diagnosis and treatment is key in reduction of its complication. Objective: To evaluate accuracy of serial C-Reactive Protein in comparison to blood culture in early diagnosis of neonatal sepsis Study design: prospective cohort study. Setting: Tertiary neonatal intensive care unit of government hospital in western UP Participants: All neonates admitted with suspicion of sepsis from July 2021 to June 2022 Intervention: Serial CRP on admission, at 12,24 and 48 hours was sent along with blood culture on admission of all the study participants.Results: Amongst 250 neonates CRP was positive in 205 patients at least on 1 occasion whereas 131 neonates were culture positive. Diagnostic accuracy of the 12 hours, 24 hours and 48 hours CRP were 50.8%, 58.4% and 65.2% to diagnose sepsis, respectively. The area under curve (AUC) of the 48-hour CRP levels was 0.826 (p<0.001), 48hour CRP was a significant predictor of neonatal sepsis. Conclusion: CRP may be used as screening test to determine newborn sepsis since it is widely accessible, affordable, and generates results quickly. Overall, serial CRP at 12, 24 and 48 hours are a useful early marker in predicting the neonatal sepsis and among them 48 hours CRP has the highest predictive capacity.