Background: The sepsis in neonates is a blood bacterial infection during the first 28 days of life. There are many common parameters that are widely used to diagnose this disease as levels of white blood cell (WBC), Procalcitonin (PCT) and C- reactive protein (CRP). Aim of work: To compare the accuracy of some laboratory parameters with blood culture for early detection of neonatal sepsis at Zagazig university children hospital. Subjects and methods: A case control study was carried out in the neonatal intensive care unit and clinical pathology department at Zagazig University Hospital, during the period from January 2019 to December 2019. This study was conducted on 15 cases had neonatal sepsis and 15 controls. All patients were subjected to the following: history talking, clinical examination, complete blood count with differential count done on peripheral blood film, quantitative measurement of the level of CRP, PCT level, blood culture and Hematological sepsis score (HSS). Results: Respiratory dysfunction was the commonest clinical presentations of sepsis. There was a significant increase in WBCs among patients than controls. Mean count of platelets in the sepsis group was significantly lowered compared with the controls. There was significant increase in HSS in sepsis group than controls. The most common organism was E. coli. PCT is more accurate in diagnosis of cases followed by CRP and WBCs, respectively. Conclusion: PCT seems to be an optimal sensitive marker for the diagnosis of neonatal sepsis.