Background: Diagnoses for neonatal sepsis are made using clinical signs and laboratory data, including cultures and non-specific infection markers like C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), and immature by total ratio (I/T ratio). We carried out this study with the objectives to correlate the progranulin (PGRN) serum level to early onset neonatal sepsis. Patients and methods: This cross-sectional study recruited 102 neonates between 34 and 40 week with early onset sepsis between May 2021 to May 2022 at tertiary referral Neonatology Unit, Pediatric Hospital, Zagazig University. Neonates (fullterm and preterm) admitted with sepsis within the first 72 hours after birth. Confirmation of neonatal sepsis was done by complete blood count, and blood culture for suspected cases. Blood samples for whole blood count, CRP, PCT and PGRN were obtained from all neonates before starting therapy. Results: This study showed that, mean value of PGRN was statistically higher among proven sepsis than not proven sepsis. While there was statistically significant decrease among proven sepsis than not proven sepsis regarding APGAR score. Regarding diagnostic accuracy of PGRN, sensitivity was 81.8%, specificity was 96.7%, PPV was 75%, NPV was 97.8% and accuracy was 95%. Regarding diagnostic accuracy of PCT, sensitivity was 72.7%, specificity was 95.6%, PPV was 66.7%, NPV was 96.7% and accuracy was 93.1%. Regarding diagnostic accuracy of CRP, sensitivity was 63.6%, specificity was 93.4%, PPV was 53.8%, NPV was 95.5% and accuracy was 90.2%. Conclusion: The use of PGRN can be good diagnostic biomarker in early onset neonatal sepsis. Its better to use PGRN combined to CRP and PCT