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Purpose: Early onset neonatal sepsis (EONS) is associated with significant morbidity and mortality in the neonatal period, so early diagnosis is crucial, and identification of reliable infection biomarkers is necessary. In this study, we aimed to evaluate the diagnostic ability of serum progranulin (PGRN) in EONS and compare its effectiveness with other conventional biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP).Patients and Methods: This prospective study was conducted between January 2021 and December 2021 at the neonatal intensive care unit, Benha University Hospital, Benha, Egypt. The study comprised 80 full-term neonates, categorized into infected and uninfected groups. Blood samples for conventional laboratory tests, blood culture and infection biomarkers were withdrawn on admission. Results: serum PGRN level was significantly higher in the infected group than uninfected group (median 89 ng/dl vs 42.95 ng/dl, respectively, p<0.0001). Using receiver operating characteristic curve analysis, the area under the curve (AUC) value of PGRN was higher than other biomarkers, as AUC was 0.836, with a 95% confidence interval (CI) of (0.758-0.979), p<0.0001 for PGRN, 0.756 (95%CI 0.647-0.845), p 0.0008 for PCT, and 0.749 (95%CI 0.639-0.839), p 0.0013 for CRP.Using a cut-off value of 43.2 ng/ml for PGRN, its sensitivity was 97%, and its negative predictive value was 95.2%. Combining PGRN and PCT increased its predictive ability; the odds ratio was 6.479 (95%CI 2.084-24.401), p=0.001.Conclusion: PGRN could be used as a promising biomarker for the diagnosis of EONS, and a combination of PGRN and PCT may enhance the diagnosis of sepsis.