Background: Sepsis has killed about 30–40% of low-income neonates, often caused by maternal-fetal microorganisms. PROM affects 3% of pregnancies, aside from chorioamnionitis, untreated UTI, etc. Many studies have predicted neonatal sepsis by detecting inflammatory markers in venous blood 12–24 hours after birth. Some studies have tested CBC, CRP, and blood culture in babies with PROM and other risk factors to predict early-onset neonatal sepsis by drawing umbilical cord blood. Hence, we performed this study to determine the role of CRP and blood cultures from umbilical cord blood to determine early-onset sepsis. Methods: This was a prospective observational study performed in Sharda university, Greater Noida. 122 neonates within 72 hours of birth born via full term vaginal delivery, after 37 completed 37 weeks of gestation. The neonates were then divided in the two groups- neonates with likely sepsis or no sepsis based on the symptoms. Following this, umbilical cord blood was drawn at 24 hours and 72 hours. Results: we observed that 32.47% of the neonates in the likely sepsis group had confirmed evidence, while 3.4% in the no sepsis group we found to have evidence of sepsis. The differences was statistically significant (p< 0.05). CRP was higher in umbilical cord blood and venous blood in likely sepsisneonates, in comparison to than blood culture yields and total WBC. Compared to the non-infected control group, the differences were statistically significant (P value 0.05). CRP demonstrated 100% sensitivity, specificity, PPV, and NPV in cord blood and 100%, 77.1%, 27.3%, and 100% in venous blood at 24 hours. Conclusion: Neonates with the higher risk of sepsis had higher readings in umbilical cord blood at birth and newborn venous blood at 24 hrs., but not at 72 hours, Also,negative CRP readings better excluded infection. Early-onset sepsis cannot be diagnosed by umbilical cord blood cultures.