Objective: To determine the presepsin and procalcitonin significance in cord blood and compare with lactate and C-Reactive protein for early prediction of neonatal sepsis. Study Design: Case Control Study. Setting: Military Hospital Rawalpindi. Period: Sep 2018 to July 2019. Methods: Mothers, having deliveries with early or prolonged rupture of membrane, preterm, dai handled, meconium and failure of induction have been included. Out of 60 neonates, nineteen were cases with a clearly documented suspicion of sepsis and confirmed by neonatologists, remaining were control. Mean and Standard Deviation were calculated. The difference in all biochemical markers levels among case and control groups were assessed by independent t-test. Sensitivity, specificity, accuracy, and predictive value of both markers were calculated by medcalc diagnostic calculator. Regression analysis to access the strength. Receiver Operating Characteristics curve for most accurate cut off values and Area Under the Curve was calculated. Results: Independent sample t test revealed the strong association of procalcitonin and presepsin with neonatal sepsis. Presepsin has higher positive predictive value 83.33% and negative predictive value 90.48% with 88.33% accuracy while procalcitonin has positive predictive value 62.50%, negative predictive value 88.89% and accuracy 78.33%. Stepwise regression analysis showed better in combination than single in predication of neonatal sepsis. The cutoff value for procalcitonin was 0.4ng/ml (AUC of 84.5%.) and for presepsin was 305pg/ml (AUC of 86.5%). Conclusion: In comparison to lactate and CRP, a prediction model that incorporates two biochemical indicators, procalcitonin and presepsin, can reduce infant mortality and morbidity by spotting neonatal sepsis early.