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 + ½ lactate); OCI], changes in mitochondrial oxygen tension (ΔPMitoO2) and the cerebral metabolic rate of oxygen (CMRO2) 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 (∼211 W). Before training, both OCI (3.9 ± 0.9) and ΔPMitoO2 (−22 mmHg) decreased ( P < 0.05), whereas CMRO2 increased by 79 ± 53 micromol·100·g−1 min−1 ( P < 0.05). At the 3-mo follow-up, OCI (4.9 ± 1.0) and ΔPMitoO2 (−7 ± 13 mmHg) did not decrease significantly from rest and when compared with values before training ( P < 0.05), CMRO2 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 maintaind cerebral oxygenation.