Background: The systemic reaction to infection in infants younger than one month old is known as neonatal sepsis. Neopterin is one of the immune activity molecular markers that is valuable for inflammatory diseases detection. Conditions with cell-mediated immune response are associated with an elevated serum neopterin levels. Objective: The current study was to assess the diagnostic value of serum neopterin level and risk factors in neonatal sepsis. Patients and methods: A case control study was conducted at Pediatrics Department of Fakous General Hospital. Case group included 24 neonates in the first 72 hours had neonatal sepsis and control group included 24 healthy neonates in the first 72 hours. Blood culture for sensitivity and measurement of serum neopterin, complete blood count and C-reactive protein were performed. Results: Regarding neopterin, cases had significantly increased neopterin levels than controls. Conclusion: In newborns with early-onset sepsis, neopterin was identified as a valuable diagnostic marker.