Abstract: Sleep and circadian disturbances may underlie cognitive dysfunction after major surgery. The aim of this study was to examine the association between sleep and circadian disturbances (as assessed by changes in the melatonin rhythm) and postoperative cognitive dysfunction (POCD). We measured subjective and objective sleep quality, excretion of the major metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s) in urine and cognitive function before and 4 days after major abdominal surgery in 36 patients. Subjective sleep quality was measured by visual analogue scale, objective sleep quality was measured by actigraphy, and cognitive function was assessed by neuropsychological testing. Eighteen patients (50%) had POCD on day 4 after surgery. At that time, the excretion of aMT6s was disturbed with significantly higher daytime excretion and a reduced night/day ratio compared with the preoperative measure (P = 0.05). Patients with POCD had significantly worse sleep quality and more night awakenings (P < 0.05) but we found no significant differences in day time (06:00–22:00 hr), night-time (22:00–06:00 hr) or total aMT6s excretion (μg/24 hr). A significant correlation was found between the total excretion of aMT6s and actigraphically measured sleep efficiency (rs = 0.45, P = 0.03) and wakefulness after sleep onset (rs = −0.44, P = 0.04). In conclusion, POCD was associated with worse subjective sleep quality and more awakenings. Circadian rhythmicity as assessed by aMT6s excretion was disturbed after surgery but we were unable to show an association with POCD. Strategies to improve postoperative sleep quality should be investigated in the future.