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Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease.To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease.In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao2), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality.During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival.In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV1, IC/TLC ratio < 0.25, and Pao2. Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.