To investigate the effects of differing levels of interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), procalcitonin (PCT), and C-reactive protein (CRP) in the early diagnosis of bacterial meningitis (BM). Methods: A total of 30 patients with bacterial meningitis were recruited as the BM group, and 30 patients with viral meningitis (VM) were assigned to the VM group. An additional 30 healthy patients were selected as the control group. The cerebrospinal fluid levels of IFN-γ, TNF-α, PCT, and CRP were measured in BM and VM groups, and blood levels of IFN-γ, TNF-α, PCT, and CRP were measured in all 3 groups. Results: Compared to the VM group, patients in the BM group showed increased cerebrospinal fluid IFN-γ content and increased TNF-α, PCT, and CRP content (P<0.05). Compared with the control group, patients in the BM group and the VM group showed decreased blood IFN-γ content and increased blood TNF-α, PCT, and CRP content (P< 0.05). Compared with the VM group, patients in the BM group displayed decreased blood IFN-γ content and increased blood TNF-α, PCT, and CRP content (P<0.05). The detection rate, accuracy and specificity of the combined assessment of IFN-γ, TNF-α, PCT, and CRP were significantly better than those of each index considered alone. Conclusion: Combined detection of IFN-γ, TNF-α, PCT, and CRP in the early diagnosis of bacterial meningitis has important clinical significance.