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Delirium is thought to be associated with systemic inflammatory response. However, its association with the most widely used inflammatory biomarker C-reactive protein (CRP) has not been well established. We aimed to examine whether CRP on intensive care unit (ICU) entry was associated with subsequent development of delirium.This prospective observational study was conducted in a mixed 24-bed ICU in a tertiary teaching hospital.All patients admitted to the ICU from February 2011 to June 2012 were screened for eligibility. Demographic data and clinical characteristics of included patients were recorded. Patients were screened for the presence of delirium by using the tool Confusion Assessment Method for the ICU (CAM-ICU). C-reactive protein was obtained on ICU entry and 24 hours thereafter. Eligible patients were followed up for 28 days or until death. Univariate and multivariate analyses were performed to evaluate independent risk factors for delirium. Clinical outcome included the length of stay (LOS) in the ICU, 28-day mortality, and duration of mechanical ventilation. Two-tailed P < .05 was considered statistically significant.A total of 223 patients were included during study period. In univariate analysis, patients with delirium showed significantly higher CRP values than those without (120.5 vs 57.5 mg/L; P = .0001). By adjusting for confounding variables (including age, sex, Acute Physiology and Chronic Health Evaluation II, intubation, living alone, physical restraint, alcohol drinking, smoking, type of medical condition, and hospital LOS before ICU admission) in logistic regression model, CRP remained an independent predictor of delirium (odds ratio, 1.07; 95% confidence interval, 1.01-1.15). As compared with nondelirious patients, those with delirium showed longer LOS in ICU (13 vs 5 days; P < .001) and duration of mechanical ventilation (6 vs 1 days; P < .001). An increase in CRP greater than 8.1 mg/L within 24 hours was associated with 4-fold increase in the risk of delirium (odds ratio: 4.47, 95% confidence interval, 1.28-15.60).C-reactive protein measured on ICU entry and its changes within 24 hours are risk indicators of delirium. Further studies exploring the treatment of delirium according to CRP levels are warranted.