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The comorbidity of HIV, tuberculosis (TB), and chronic kidney disease (CKD) significantly worsens health outcomes and complicates care in low-resource settings. This study assessed the burden of co-morbidity of HIV, TB, and CKD among patients in the Sekyere South Municipal. A cross-sectional study was conducted from July to December 2024 at the Seventh-Day Adventist Hospital, Agona-Asamang. A total of 183 HIV and/or TB patients aged 18–80 was purposively recruited along with 81 healthy controls. Data collection included questionnaires, medical record reviews, and laboratory tests. HIV was diagnosed using rapid tests, TB via GeneXpert, and CKD using serum urea/creatinine and eGFR (CKD-EPI). Data were analysed using SPSS v23.0. HIV-TB coinfection prevalence was 19.13% (35/183); 68.6% were female (24/35). Among them, 88.57% (31/35) had CKD—67.7% of whom were female (21/31). Age (OR=1.038; p=0.045), alcohol use (OR=19.075; p=0.011), and hypertension (OR=16.520; p=0.037) were significant CKD risk factors. HIV-TB-CKD patients had significantly higher creatinine (p=0.020), lower eGFR (p=0.044), reduced haemoglobin and haematocrit (p<0.001), and elevated monocytes (p<0.001), indicating inflammation. Mortality among the HIV-TB-CKD group was 16.1%, with hospitalizations common but not significantly improving outcomes (χ²=11.454). HIV, TB, and CKD comorbidity is common and disproportionately affects women. Integrated screening, early diagnosis, and management of risk factors are essential. Findings support multisectoral strategies to strengthen HIV care systems in line with SDG 3 and WHO sector goals.