Pneumococcal conjugate vaccine (PCV13) introduction has reduced vaccine-type carriage and disease; however pneumococcal carriage persists at high rates particularly in high-transmission settings. Serotype 3 remains a particular problem in Malawi and globally, with high carriage rates, as well as strain resistance to antibiotics and antibody-mediated killing. We studied antibody and B cell responses to PCV13 in 65 healthy Malawian adults (18-40 years) taking part in a randomized controlled trial. Serum, nasal fluid, and PBMC samples were collected before and after vaccination. Anti-capsular IgG for serotypes 3 and 6B were measured by ELISA, and capsule-specific B cells were assessed by spectral flow cytometry. PCV13 increased both serum and mucosal IgG levels, and IgG+ B cells in blood for serotype 6B but not serotype 3. The poor immunogenicity of serotype 3 capsular polysaccharide in Malawian young adults highlights the need for alternative vaccines to address persistent serotype 3 carriage and disease.