Background: Neonatal sepsis is one of the major causes of neonatal morbidity and mortality and is often difficult to distinguish from many other conditions. Thus investigating new markers for early and prompt diagnosis of sepsis in neonates is a major concern. The purpose of this study was to investigate the role of plasma gelsolin level as a potential marker in the diagnosis of early neonatal sepsis. Methods: This case control study was carried out in the Intensive Neonatal Care Unit (NICU), Microbiology and Immunology Department, Zagazig University children hospital during the period from March 2018 to February 2019. 46 neonates were included in the study. There were divided randomly into two groups. Group 1 included 23 septic neonate group and group 2 included 23 apparently healthy sex and age-matched neonates served as a control group. All patients were evaluated clinically and investigated for routine laboratory workup and sepsis markers in addition to plasma gelsolin level using ELISA technique. Results: The most important risk factors for sepsis were premature rupture of membrane (PROM), which was found in 30.4% and maternal fever in 26.1% in septic group. The mean value of Plasma gelsolin was found significantly lower among cases in comparison to the controls group. Conclusions: Plasma gelsolin could be used as a reliable diagnostic marker of early neonatal sepsis