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• Elevated high-sensitivity C-reactive protein levels were associated with TB test results in HIV-positive Kenyan patients. • Malnutrition and elevated HS-CRP were found to be associated with TB in HIV-positive patients. • Combined malnutrition and elevated HS-CRP waere correlated with short-term mortality, especially in TB-negative patients. • HS-CRP could play a role in HIV care services as a predictor of TB infection and short-term mortality. Tuberculosis (TB) is the leading cause of death in HIV-positive people. In Kenya, 140 000 new TB cases occurred in 2019, and 13 000 HIV-positive patients died due to TB. The objective of this study was to investigate the role of high-sensitivity C-reactive protein (HS-CRP) in TB diagnosis and the prediction of mortality in HIV-positive patients. The IDEA-TB Study enrolled HIV-positive adult patients attending three DREAM centres in Kenya who were suspected of having TB. A lateral flow urine lipoarabinomannan assay (LF-LAM), serum HS-CRP, and GeneXpert MTB/RIF assay (Xpert MTB/RIF) were performed. Six-month survival was evaluated. A total of 574 patients were enrolled. The median (interquartile range) age, body mass index, and CD4 count were 45 years (37–54 years), 20.5 kg/m2 (18.5–23.69 kg/m2), and 477 cells/mL (290–700 cells/mL), respectively. TB was confirmed in 87 (15.2%) patients. Concordance between the Xpert MTB/RIF and LF-LAM tests was 87.1%. HS-CRP was higher in TB patients (35.39 mg/l vs 9.21 mg/l). Malnutrition and elevated HS-CRP were associated with TB: odds ratio (OR) 2.5 (95% confidence interval (CI) 1.14–5.72) and OR 6.6 (95% CI 3.87–11.52), respectively. Nine (1.6%) patients died during follow-up. No single factor was associated with mortality. Only the combination of malnutrition and elevated HS-CRP was highly predictive of death (odds ratio (OR) 9.8, 95% CI 1.88–50.95); the association was stronger in TB patients (33.3% vs 1.0%; OR 47.6, 95% CI 7.03–322.23). TB diagnosis in HIV-positive patients remains challenging. HS-CRP could play a role in predicting early mortality in symptomatic patients. [ABSTRACT FROM AUTHOR]