Background: Meningitis is an inflammation of the leptomeninges. The inflammation may be caused by infection with viruses, bacteria, other micro-organisms, or non-infective causes. Objective: The aim of this study was to evaluate the role of CSF-Presepsin in diagnosis of bacterial meningitis and in differentiation between bacterial and viral meningitis or aseptic meningitis. Patients and methods: The present study was a cross sectional study conducted in Intensive Care Unit and Pediatric Departments of El-Hommyat Hospital in Zagazig in the period from January 2017 to November 2017. The study included 50 patient of children with age from 6 months to 14 years with symptoms of CNS infection. Among the studied subjects there were 30 cases already diagnosed as bacterial meningitis and 20 cases already diagnosed to have viral meningitis (controls). Full history, clinical examination, and full laboratory tests were taken (Complete blood count (CBC) with differential leukocytic count, random blood sugar, serum CRP, and CSF analysis, CSF presepsin (psp) and CRP). Results: There was a significant increase in Presepsin and CRP in the CSF of cases of bacterial when compared to viral group. Additionally, there were significant direct correlation between CSF presepsin and CSF CRP to blood CRP, CSF total leucocytic count (TLC) and CSF protein and indirect correlation between CSF presepsin and hemoglobin level, platelet count and CSF glucose. Conclusion: CSF-Presepsin and CSF-CRP can be used in diagnosis of bacterial meningitis and can differentiate between them in bacterial and viral patients.