Purpose Preexercise ingestion of exogenous ketones alters the metabolic response to exercise, but effects on exercise performance have been equivocal. Methods On two occasions in a double-blind, randomized crossover design, eight endurance-trained runners performed 1 h of submaximal exercise at approximately 65% VO2max immediately followed by a 10-km self-paced time trial (TT) on a motorized treadmill. An 8% carbohydrate-electrolyte solution was consumed before and during exercise, either alone (CHO + PLA), or with 573 mg center dot kg(-1) of a ketone monoester supplement (CHO + KME). Expired air, HR, and RPE were monitored during submaximal exercise. Serial venous blood samples were assayed for plasma glucose, lactate, and beta-hydroxybutyrate concentrations. Results CHO + KME produced plasma beta-hydroxybutyrate concentrations of approximately 1.0 to 1.3 mM during exercise (P < 0.001), but plasma glucose and lactate concentrations were similar during exercise in both trials. VO2, running economy, respiratory exchange ratio, HR, and RPE were also similar between trials. Performance in the 10-km TT was not different (P = 0.483) between CHO + KME (mean, 2402 s; 95% confidence interval, 2204-2600 s) and CHO + PLA (mean, 2422 s; 95% confidence interval, 2217-2628 s). Cognitive performance, measured by reaction time and a multitasking test, did not differ between trials. Conclusions Compared with carbohydrate alone, coingestion of KME by endurance-trained athletes elevated plasma beta-hydroxybutyrate concentrations, but did not improve 10-km running TT or cognitive performance.