Objective: The effects of cardiopulmonary bypass (CPB) on serum neuron-specific enolase (NSE) levels in patients without cognitive dysfunction and neurological deficit are not yet clarified. This study was designed to see the sole effect of extracorporeal circulation on serum NSE levels in patients without any clinically observed neurological deficit. Methods: Thirty-two consecutive patients undergoing first elective open-heart surgery were included in this prospective study. Neurological status was assessed by clinical examination before surgery, and on the postoperative first and second days. Blood samples were obtained after anesthesia induction before the administration of heparin, within the first hour post CPB, 24 and 48 hours after the end of operation. Each blood sample was assayed for hemoglobin (Hb), hematocrit and NSE levels. The Friedman's Test to compare the serial measurements of NSE and hemoglobin samples and the post-hoc Tukey test for paired comparisons between pre and postoperative values were applied Pearson correlation test was used to examine the correlation between NSE concentration and aortic cross-clamping time and CPB time, age, postoperative hematocrit and hemoglobin levels and the amount of blood products transfusion. Results: There were no significant differences between NSE values at any sampling time: 11.6±8.0 mg/dL, 8.7±4.7 mg/dL, 9.3±5.4 mg/dL and 8.9±5.8 mg/dL, measured preoperatively, at the end of operation, on the first and second post-operative days, respectively. There was no significant correlation between NSE values with any of the compared variables including CPB time. Conclusion: This study demonstrated that the possible damage of CPB on central nervous system and on blood cells did not reach to the extent of causing any significant increase in serum NSE levels in non-complicated patients undergoing open-heart surgery.