Pneumococcal vaccination schedules are traditionally assessed based on the antibody response. The Memory B Cell (MBC) response has been less studied, despite its role in the magnitude and longevity of protection. We compared the immune response to different vaccination schedules with the 13-valent Pneumococcal Conjugate Vaccine (PCV13) and investigated the relationship between MBCs and the antibody response. Total and pneumococcal serotype (PS)-specific MBCs, their subsets and PS-specific IgG antibodies induced by a 3 + 0 (group A), 2 + 1 (group B) or 3 + 1 (group C) schedule in healthy infants were studied before and 1 month after the last PCV13. The relatively immature IgM+IgD+ MBC subset was the predominant subset in all groups but was larger in group A compared to group B and group C, indicating that age might be a significant parameter of the composition of the MBC pool. PS-specific MBCs at baseline were higher in group A, but they increased significantly only in the groups receiving the booster schedules (groups B and C). PS-specific IgM-only MBCs at baseline positively corelated with the antibody response and the PS-specific swIg MBCs post-immunization. Our findings illustrate the importance of a booster dose for the enrichment of PS-specific immunological memory. IgM-only MBCs and swIg MBCs may serve as additional correlates of vaccine-induced protection.