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In resource-limited settings, mortality in the initial months following antiretroviral therapy (ART) initiation remains unacceptably high. Novel tools to identify patients at highest risk of poor outcomes are needed. We evaluated whether elevated C-reactive protein (CRP) concentrations predict poor outcomes among people living with HIV (PLWH) initiating ART.We enrolled and followed for 3-months consecutive PLWH with pre-ART CD4+ T-cell counts 350 cells/μl or less initiating ART from two HIV clinics in Uganda. Pre-ART CRP concentrations were measured from capillary blood using a point-of-care (POC) assay. After excluding patients with prevalent tuberculosis – the leading cause of HIV death – we measured 3-month mortality rates using Kaplan–Meier curves, used Cox regression to compare differences in survival, and used logistic regression to compare differences in the odds of opportunistic infections, between patients with and without elevated POC CRP (≥8 mg/l).Of 1293 patients included [median CD4+ T-cell count 181 (interquartile range 82–278)], 23 (1.8%) died within 3 months, including 19 of 355 (5.4%) with elevated POC CRP and four of 938 (0.4%) with nonelevated POC CRP. Eighty-six (6.7%) patients were diagnosed with opportunistic infections, including 39 of 355 (11.0%) with elevated POC CRP and 47 of 938 (5.0%) with nonelevated POC CRP. Elevated POC CRP was associated with mortality (adjusted hazard ratio 10.87, 95% confidence interval 3.64–32.47) and opportunistic infection (adjusted odds ratio 1.95, 95% confidence interval 1.23–3.07).Among PLWH with advanced HIV, elevated pre-ART POC CRP concentrations are associated with early mortality and opportunistic infections. Pre-ART POC CRP testing may reduce mortality by identifying patients at high risk for poor outcomes.