OBJECTIVE: Indonesia commenced the nationwide introduction of pneumococcal conjugate vaccine (PCV) in 2022. Pre-vaccine Streptococcus pneumoniae data from across the country could be critical to enable vaccine impact evaluation in the future. This study evaluates colonization prevalence, factors associated with colonization, serotype distribution, and the antimicrobial susceptibility profile of S. pneumoniae. METHODS: Children under 5 years of age were enrolled from Bajau tribe settlements in Wakatobi, southeast Sulawesi, Indonesia, from October 2018 to February 2019. Nasopharyngeal swab specimens were analysed by culture, and isolates were serotyped using sequential multiplex polymerase chain reaction. Antibiotic susceptibility was performed by the disk diffusion method. Multivariable logistic regression was performed for risk factor analysis. RESULTS: A total of 499 NP swab specimens were collected; 61.9% were colonized with S. pneumoniae and 48.9% of the isolates were of PCV13-vaccine type. The most common serotypes were 23F, 6B, 19F, and 6A at 13.2%, 9.8%, 8.9%, and 8.0%, respectively. Exposure to cigarette smoke in the household and runny nose were significant risk factors for colonization, with aORs of 1.6 (95% confidence interval: 1.1-2.3) and 2.1 (95% confidence interval: 1.4-3.3), respectively. CONCLUSIONS: The findings of this study may contribute to baseline pre-vaccine data in Indonesia that would be critical for the impact evaluation of vaccines.