Melatonin, a neurohormone, plays an important role in adjusting the "biological clock" in humans. We sought to describe perioperative patterns of melatonin secretion in patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass (CPB). After IRB approval and written informed consent, 12 male patients scheduled for elective coronary artery bypass grafting under hypothermic CPB were enrolled in the study. During anesthesia, patients' eyes were carefully covered to prevent light effects. Blood samples were taken at specific time points during surgery, every 3 h in the immediate postoperative period, and for 24 h from 6:00 PM of Postoperative Day 2 until 6:00 PM of Postoperative Day 3. Plasma melatonin and cortisol concentrations were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. During surgery, plasma melatonin concentrations were below the minimum sensitivity concentration, yet small concentrations, without circadian variation, were detected during the immediate postoperative period. During Postoperative Days 2 and 3, circadian secretion patterns of melatonin were present in 10 patients and showed an inverse correlation with light intensity (r = 0.480; P < 0.01). Plasma cortisol concentrations in the immediate postoperative period were significantly larger than those before the induction of anesthesia (P < 0.01). Only three patients regained circadian secretion of cortisol. We concluded that melatonin and cortisol secretion was disrupted during cardiac surgery with CPB and in the immediate postoperative period. However, circadian rhythms of melatonin were present in most patients from Postoperative Day 2. Only 30% of the patients regained circadian rhythm of cortisol secretion. Melatonin is a hormone that plays an important role in adjusting the biological clock in humans and that regulates secretion of various other hormones. We studied melatonin secretion in patients undergoing cardiac surgery with cardiopulmonary bypass. Melatonin secretion was disturbed during and immediately after surgery but had recovered a circadian rhythm 24 h later, raising the question of whether melatonin should be supplemented before cardiac surgery.