Background. To better understand the high incidence of pneumococcal meningitis in the African meningitis belt, we conducted a pneumococcal seroprevalence study during a meningococcal meningitis epidemic in Western Burkina Faso, March 2006. Methods. In 3 villages experiencing epidemics, we included 624 healthy persons (1–39 years) by cluster sampling. We determined pneumococcal serum immunoglobulin G (IgG) antibody concentrations against 12 serotypes contained in 13-valent pneumococcal conjugate vaccine, and evaluated determinants for IgG ≥ 0.35 μg/mL by multivariate logistic regression. Results. The percentage of subjects with serotype-specific IgG concentrations ≥0.35 μg/mL increased with age and was similar for the different serotypes: it was 20%–43% among 1–4-year-olds and 56%–90% among 20–39-year-olds. Prevalence of IgG ≥ 0.35 μg/mL against serotype 1 was up to 71% after age 10 years. During multivariate analyses, determinants of IgG concentrations ≥0.35 μg/mL varied by serotype; for 5 and 6 serotypes, respectively, female sex (around 2-fold increased odds) and cigarette smoking (about 5-fold reduced odds) predicted elevated titers. Conclusions. Despite a substantially higher historical pneumococcal meningitis incidence in Burkina Faso, the general population has an antibody seroprevalence against 12 pneumococcal serotypes similar to that reported from the United Kingdom. The role of putatively protective antibody seroprevalence in preventing pneumococcal meningitis in the meningitis belt requires more thorough evaluation.