Background: Distinguishing septic and aseptic meningitis in the emergency department could help limit unnecessary antibiotic use and hospital admissions. Objectives: To assess the potential diagnostic role of serum and cerebrospinal fluid (CSF) neopterin and complement 3 (C3) levels as a rapid diagnostic method for differential diagnosis of septic and aseptic meningitis. Methodology: Forty patients with proven acute meningitis, were categorized into 2 groups, Group I: 20 patients with septic (bacterial) meningitis as confirmed by CSF analysis and positive Gram stain and/or conventional bacterial culture; Group II: 20 patients with proved aseptic meningitis (viral and fungal) as confirmed by CSF analysis with negative culture for bacteria. Serum/CSF neopterin was assayed by Enzyme Linked Immunosorbent Assay (ELISA) while C3 level in serum was assayed by single radial immune diffusion. Results. The simultaneous elevation in serum and CSF neopterin shows high significance in the diagnosis of septic meningitis cases (P < 0.001). Conclusion. The combined elevated serum and CSF neopterin has a remarkable application in the diagnosis of bacterial meningitis, and can thus help differentiate bacterial from aseptic meningitis