We assessed the development and role of serum anti-CbpA and -PhtD in early childhood in relation to pneumococcal exposure. Serum IgG concentrations to CbpA and PhtD were measured with enzyme immunoassay in serum samples collected at the ages of 6, 12, 18, and 24 months from 50 healthy children and from 50 adults. Furthermore, antibodies to CbpA, PhtD and the C-terminal fragment of PhtD (PhtD C) were measured in serum samples collected at 12 (N=286) and 18 months (N=259) to evaluate the risk of subsequent pneumococcal acute otitis media (AOM) in relation to antibody concentrations. The increase in anti-CbpA and -PhtD concentrations was related to prior pneumococcal exposure. At 12 and 18 months, in the risk model of pneumococcal AOM adjusted for prior pneumococcal AOM, higher concentrations of anti-CbpA, but not anti-PhtD, were associated with a lowered risk of subsequent pneumococcal AOM. In conclusion, pneumococcal exposure induces the development of serum anti-CbpA and -PhtD in early childhood. Anti-CbpA antibodies may play a role in the prevention of subsequent pneumococcal AOM during the second year of life.