BACKGROUND Near-infrared spectroscopy (NIRS) is used routinely to monitor cerebral tissue oxygen saturation ( S ctO 2 ) during cardiopulmonary bypass (CPB) but is rarely employed outside the operating room. Previous studies indicate that patients are at risk of postoperative cerebral oxygen desaturation after cardiac surgery. OBJECTIVES We aimed to assess perioperative and postoperative changes in NIRS-derived S ctO 2 in cardiac surgery patients. DESIGN Prospective observational study. SETTING The study was conducted in a tertiary referral university hospital in Australia from December 2017 to December 2018. PATIENTS We studied 34 adult patients (70.6% men) undergoing cardiac surgery requiring CPB and a reference group of 36 patients undergoing non-cardiac surgical procedures under general anaesthesia. MAIN OUTCOME MEASURES We measured S ctO 2 at baseline, during and after surgery, and then once daily until hospital discharge, for a maximum of 7 days. We used multivariate linear mixed-effects modelling to adjust for all relevant imbalances between the two groups. RESULTS In the cardiac surgery group, S ctO2 was 63.7% [95% confidence interval (CI), 62.0 to 65.5] at baseline and 61.0% (95% CI, 59.1 to 62.9, P = 0.01) on arrival in the ICU. From day 2 to day 7 after cardiac surgery, S ctO 2 progressively declined. At hospital discharge, S ctO 2 was significantly lower than baseline, at 53.5% (95% CI, 51.8 to 55.2, P < 0.001). In the reference group, postoperative S ctO 2 was not significantly different from baseline. On multivariable analysis, cardiac surgery, peripheral vascular disease and time since the operation were associated with greater cerebral desaturation, whereas higher haemoglobin concentrations were associated with slightly better cerebral oxygenation. CONCLUSION After cardiac surgery on CPB, but not after non-cardiac surgery, most patients experience prolonged cerebral desaturation. Such postoperative desaturation remained unresolved 7 days after surgery. The underlying mechanisms and time to resolution of such cerebral desaturations require further investigation.