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Objectives: The value of measurements of serum C-reactive protein (CRP) in differentiating central nervous system (CNS) infections of varying etiologies in the Philippines was investigated. Methods: A wide array of bacteriologic and virologic methods as well as computed tomography, typical clinical presentation, and autopsy were used for etiologic diagnosis. Results: Among 103 patients with CNS infection, etiology was identified in 60 (58%) cases. Bacteria were found in 19 (including 7 Streptococcus pneumoniae, 5 Haemophilus influenzae, 3 Neisseria meningitidis), tuberculosis in 4, viruses in 38 (including 20 coxsackievirus, 8 measles, 4 adenovirus, and 4 poliovirus infections), and brain abscess in 3 patients. C-reactive protein was elevated on admission in all 18 cases of bacterial meningitis tested, exceeding 50 mg/L in 17 (94%), and was not affected by prior antibacterial treatment. The mean CRP was significantly higher in the bacterial group than in the viral group (207 ± 111 mg/L vs. 39 ± 34 mg/L; P < 0.001). In the viral group one third had CRP above 50 mg/L. In patients with tuberculous meningitis, brain abscess, or cryptococcal meningitis, CRP was moderately to highly elevated. Conclusions: In the presence of a normal CRP concentration (below 10 mg/mL) acute bacterial meningitis is excluded even in a developing country setting and antimicrobial therapy is not warranted.