Backgound: Neonatal sepsis is defined as a clinical syndrome of bacteremia with signs and symptoms of infection in the first four weeks of life. A better understanding of the neonatal inflammatory response to sepsis and identification of sensitive and specific markers of inflammation or rapid microbe-specific diagnostic tests would assist in the early detection of neonatal sepsis. Objective: Evaluate of serum neopterin level as an early diagnostic marker in neonatal sepsis for early detection of neonatal sepsis and early implementation of the appropriate therapeutic strategies. Patients and Methods: The current study included 90 newborns admitted into NICU with 30 of them septic, 30 suspected neonatal sepsis and 30 control at Aswan University Hospital during the study period after obtaining consent from the parents. Results: Neopterin level was significantly higher in cases than control (p < 0.001). A highly significant positive correlations was found between serum neopterin with TLC, T. neutrophils, immature/total neutrophil (I/T) ratio, serum C-reactive protein (CRP) level, ESR 1st hour, ESR 2nd hour and sepsis score. On the other hands, negative correlation was found between serum neopterin level and gestational age, with poor Moro reflex & apnoea. Moreover, no significant relation was found between serums level of neopterin and socio-demographic data. Conclusion: Combined use of one or more laboratory marker as Haematological scoring system (HSS) and CRP with neopterin will enhance the diagnostic accuracy, early detection and consequently prevention of complications of infected cases.