Background: Early management is necessary for neonatal sepsis (NS), a clinical disease that may be life-threatening. Initial symptoms are frequently vague and might resemble a number of other medical disorders. In newborn populations, NS is a significant cause of death and morbidity. Objective: The objective of this study was to study Mean Platelet Volume (MPV) in diagnosis and of neonatal sepsis. Patients and Methods: This study was a case control study which conducted at Neonatology unit, Pediatrics department, Zagazig University Hospitals.Mean Platelet Volume were measured for all neonates. Results: There was no statistically significant difference between cases group and controls groupregarding demographic data. There was statistically positive correlation between MPV and WBCs and negative correlation between MPV and (Apgar score). MPV showed a significant negative correlation with gestational age, birth weight, platelet count, whereas it showed statistically significant positive correlation with CRP and the I/T ratio. In this study, regarding Diagnostic accuracy of MPV, Sensitivity was 96.7%, Specificity was 93.3%, PPV was 67.4%, NPV was 50% and accuracy was 66.7%. Conclusion: MPV increases significantly in neonates with sepsis. MPV could be a useful as early diagnostic marker in neonatal sepsis.