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OBJECTIVES To investigate an association between the preoperative plasma B-type natriuretic peptide (BNP) concentration and cerebral regional saturation (rSO2) measured using the INVOS oximeter (Medtronic, Minneapolis, MN). DESIGN A retrospective data analysis. SETTING Single university hospital. PARTICIPANTS Patients undergoing off-pump coronary artery bypass (OPCAB) surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Associations of variables obtained from preoperative blood laboratory tests and transthoracic echocardiography with baseline rSO2 before induction of general anesthesia were investigated using bivariate and multivariate regression analyses in 330 OPCAB patients. With bivariate analyses, age; body size-related variables such as weight and body surface area; hematologic function-related variables such as blood hemoglobin (Hb) concentration and arterial oxygen saturation; renal function-related variables including estimated glomerular filtration rate, creatinine, and blood urea nitrogen; hepatic function-related variables including cholinesterase, albumin, total bilirubin, and alanine aminotransferase; serum electrolytes including sodium, chloride, and phosphorus; BNP or log-transformed BNP; and 13 transthoracic echocardiography variables such as left ventricular ejection fraction highly significantly correlated with baseline rSO2 (p < 0.0001). However, the multiple regression analysis revealed that only BNP and Hb remained major factors significantly associated with baseline rSO2 (p < 0.0001), while estimated glomerular filtration rate, arterial oxygen saturation, and body surface area remained minor factors (p < 0.05). Baseline rSO2 correlated better with log-transformed BNP than with BNP, indicating that rSO2 correlated with BNP in an exponential fashion. CONCLUSIONS Preoperative BNP and Hb concentrations were 2 major factors associated with INVOS rSO2 in patients undergoing OPCAB.