Endurance training improves muscular and cardiovascular fitness, but the effect on cerebral oxygenation and metabolism remains unknown. We hypothesized that 3 mo of endurance training would reduce cerebral carbohydrate uptake with maintained cerebral oxygenation during submaximal exercise. Healthy overweight males were included in a randomized, controlled study (training: n = 10; control: n = 7). Arterial and internal jugular venous catheterization was used to determine concentration differences for oxygen, glucose, and lactate across the brain and the oxygen-carbohydrate index [molar uptake of oxygen/(glucose + (1/2) lactate); OCI], changes in mitochondrial oxygen tension (DeltaP(Mito)O(2)) and the cerebral metabolic rate of oxygen (CMRO(2)) were calculated. For all subjects, resting OCI was higher at the 3-mo follow-up (6.3 +/- 1.3 compared with 4.7 +/- 0.9 at baseline, mean +/- SD; P < 0.05) and coincided with a lower plasma epinephrine concentration (P < 0.05). Cerebral adaptations to endurance training manifested when exercising at 70% of maximal oxygen uptake (approximately 211 W). Before training, both OCI (3.9 +/- 0.9) and DeltaP(Mito)O(2) (-22 mmHg) decreased (P < 0.05), whereas CMRO(2) increased by 79 +/- 53 micromol x 100 x g(-1) min(-1) (P < 0.05). At the 3-mo follow-up, OCI (4.9 +/- 1.0) and DeltaP(Mito)O(2) (-7 +/- 13 mmHg) did not decrease significantly from rest and when compared with values before training (P < 0.05), CMRO(2) did not increase. This study demonstrates that endurance training attenuates the cerebral metabolic response to submaximal exercise, as reflected in a lower carbohydrate uptake and maintained cerebral oxygenation.