Background: Inadequate depth of anesthesia leads to release of stress hormones. Electroencephalographic monitoring by bispectral index is a guide to asses the depth of anesthesia. The aim of the present study was to measure the serum cortisol levels as an index of stress response in patients who are candidates for coronary artery bypass graft surgery in two groups of patients. Methods: Seventy-six patients who were scheduled for primary elective cardiopulmonary bypass were enrolled in a double–blind randomized study. The patients were divided into two groups. The infusion of anesthetic drugs was guided by bispectral index in group I (n=38), and by clinical judgment in group II (n=38). For all the patients the blood cortisol level was measured four times during operation. Results: Serum cortisol levels decreased during operation in both groups, reaching 67.8% of the baseline in group I and 63.2% of the baseline in group II. There were no significant differences in mean serum cortisol levels between the two groups (p<0.09). Preoperatively, the mean blood cortisol level was 19.94 mg/dl in group I and 16.89 mg/dl in group II which reached to 10.48 mg/dl in group I and 6.42 mg/dl in group II postoperatively. There was no significant difference between two groups regarding bispectral index values. Conclusions: It seems that monitoring of the patients by clinical judgment or bispectral index has equal influences on serum cortisol levels during coronary artery bypass graft surgery.