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We tested the hypothesis that elevated postoperative interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations are associated with short- and medium-term impairment of cognitive functions in patients after coronary artery surgery using cardiopulmonary bypass. Eighty-six age- and education-balanced patients ≥55 years of age undergoing elective coronary artery bypass surgery with cardiopulmonary bypass and 28 nonsurgical controls with coronary artery disease were enrolled. Recent verbal and nonverbal memory and executive functions were assessed before surgery and at 1 week and 3 months after surgery using a cognitive test battery. IL-6 concentrations were measured before surgery and 4 h after cardiopulmonary bypass, and CRP concentrations were measured before surgery and at 24 and 72 h after anesthetic induction. Overall cognitive function between high and low biomarker concentration groups was analyzed by the Wilcoxon rank-sum test. Recent memory was at least 1 standard deviation (SD) impaired at 1 week and 3 months in the high-CRP compared with low-CRP and in the high-IL-6 compared with low-IL-6 concentration groups. Overall cognitive function was significantly (P = 0.04 and P = 0.01, respectively) different between the high- and low-CRP concentration groups (CRP assayed 24 h after anesthetic induction) at both 1 week and 3 months. Overall cognitive function was also significantly (P = 0.04) different between the high- and low-IL-6 concentration groups at 1 week after surgery. The results suggest that elevated postoperative IL-6 and CRP concentrations are associated with the subsequent development of short- and medium-term impairment of cognitive functions after coronary artery surgery.