1-(1) C5 genotype rs17611 was associated with worse outcome in pneumococcal meningitis patients (OR 2.25; 95% CI 1.33–3.81; P = 0.002). Patients with rs17611 GG genotype) had lower CSF WBC counts. 1-(2) C5a and MAC levels in CSF correlated with admission, death, and worse outcome. 2-(1) CSF WBC count was lower in C5aR deficient compared to WT mice. While C5aR deficient mice exhibited reduced clinical scores, there was no difference in cerebellar bacterial titers. 2-(2) Anti-C5 antibody treatment was protective against pneumococcal meningitis. The gene discussed is C5AR1; the disease is pneumococcal meningitis.