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Aims: To compare nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae among patients with and without diabetes at Moi Teaching and Referral Hospital (MTRH) in western Kenya., Methods: A cross-sectional study was conducted at MTRH diabetes and eye clinics. Participants were selected using systematic random sampling. Sociodemographic data and risk factors were collected through interviewer-administered questionnaires. Blood samples were taken to measure random blood sugar and HbA1c levels. Nasopharyngeal swabs were cultured and tested for antibiotic susceptibility within 24 h. Data analysis was performed using STATA version 13. Associations were assessed using Pearson's chi-square, Fisher's exact test, unpaired t-test, and Wilcoxon test., Results: A total of 124 participants with diabetes and 121 without diabetes were enrolled. Overall, 7.4 % (95 % CI: 4.4, 11.4) of participants carried S. pneumoniae. Carriage was higher in diabetes (12.1 % [95 % CI: 7.0, 19.0]) than non-diabetes participants (2.48 % [95 % CI: 1.0, 7.0]), with a statistically significant difference (p = 0.004). Diabetes was associated with higher odds of carriage (adjusted OR 6.2, p = 0.012). No association was found with age, sex, cooking fuel, presence of children under 5, or prior antibiotic use. Among participants with diabetes, carriage of Streptococcus Pneumoniae was only associated with insulin use. Antibiotic resistance was highest for cotrimoxazole (94.44 %), followed by amoxicillin (16.7 %) and cefuroxime (11.1 %). No resistance to macrolides was observed., Conclusion: Nasopharyngeal carriage of S. pneumoniae is higher in patients with diabetes, with significant resistance to common antibiotics, though macrolides remain effective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)