Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy people and causes otitis media, pneumonia, bacteremia, and meningitis. In this study, we analyzed an S. pneumoniae strain that caused 7 repeated pneumonia episodes in an 80-month-old patient with cerebral palsy during a period of 25 months. A total of 10 S. pneumoniae strains were obtained from sputum samples, and serotype 6B was isolated from samples from the first 5 episodes, whereas serotype 6A was isolated from samples from the last 2. Whole-genome sequencing showed clonality of the 10 isolates with 10 single nucleotide polymorphisms (SNPs) in the genomes. Among these SNPs, one single point mutation in the wciP gene was presumed to relate to the serotype switching from 6B to 6A, and the other mutations in parC and gyrA were related to fluoroquinolone resistance. These results suggested that an S. pneumoniae strain, which asymptomatically colonized the patient's nasopharynx or was horizontally transmitted from an asymptomatic carrier, caused the repeated pneumonia events. Phenotypic variations in the capsule type and antimicrobial susceptibility occurred during the carrier state. Hyporesponsiveness to serotypes 6B and 6A of S. pneumoniae was found even after vaccination with the 7-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. After an additional vaccination with the 13-valent pneumococcal conjugate vaccine, opsonic activities for both serotypes 6A and 6B significantly increased and are expected to prevent relapse by the same strain.