Background Delirium is an acute mental disorder and common postoperative complication. Monitoring regional cerebral oxygen saturation (rSO(2)) in endovascular therapeutic surgery may allow real-time monitoring of cerebral desaturation, avoiding profound cerebral dysfunction, and reducing the incidence of delirium. We sought to examine the incidence of delirium in patients undergoing endovascular surgery. Methods This was a clinical cohort trial (registered with [NCT02356133]). We monitored the rSO(2) of 43 patients undergoing general anesthesia and cerebral endovascular surgery. The occurrence of delirium after surgery was recorded with the Confusion Assessment Method (CAM). Multivariate logistic regression was performed to identify the main predictor of delirium. Results rSO(2) was significantly different between the delirium and no-delirium groups. The occurrence of delirium was 35% in our cohort, and higher rSO(2) desaturation scores were significantly associated with profound delirium (higher CAM score; odds ratio = 1.002; P = 0.021). The maximum declines of systolic blood pressure were 24.86 (21.78-27.93) and 32.98 (28.78-37.19) in the no-delirium and delirium groups, respectively, which were significantly different (P = 0.002) but not closely associated with delirium in multivariate analysis (P = 0.512). Anesthesia, mechanical ventilation duration, and having two vascular risk factors differed significantly between groups but were poorly associated with delirium outcome. Conclusions Elevated rSO(2) desaturation score was predictive of the occurrence of postoperative delirium following endovascular surgery. Monitoring rSO(2) is invaluable for managing controlled hypotension during endovascular surgery and reducing postoperative delirium.