Background: Neonatal sepsis is the medical term for a bloodstream infection in newborn infants younger than 28 days old. Procalcitonin (PCT) and C-reactive protein (CRP), are non-specific infection markers, which are being employed as biomarkers to help diagnose neonatal sepsis.This study aimed to correlate the progranulin (PGRN) serum level to early onset neonatal sepsis (EOS). Patients and methods: This cross-sectional study was carried out at tertiary referral Neonatology Unit, Pediatric Hospital and Medical Biochemistry Department, Zagazig University during the period from May 2021 to May 2022. Confirmation of neonatal sepsis was done by total blood count and, in cases of suspicion, blood culture. All neonates had their blood drawn for whole blood count, CRP, PCT, and PGRN testing prior to beginning treatment. Results: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PGRN diagnostic test were 81.8%, 96.7%, 75.5%, and 95.5%, respectively. PCT has a sensitivity of 72.7%, specificity of 95.6%, PPV of 66.7%, NPV of 96.7%, and accuracy of 93.1% in terms of diagnostic accuracy. Sensitivity, specificity, PPV, NPV, and accuracy of CRP diagnostics were all above average. Conclusion: PGRN may be used as biomarker for EOS diagnosis.