Fatigue resulting from strenuous exercise can impair cognition and oculomotor co
ntrol. These impairments can be prevented by administering psychostimulants such
as caffeine. This study used two experiments to explore the influence of caffei ne administered at rest and during fatiguing physical exercise on spatial attent ion-a cognitive function that is crucial for task-based visually guided behavior . In independent placebo-controlled studies, cohorts of 12 healthy participants consumed caffeine and rested or completed 180 min of stationary cycling. Covert attentional orienting was measured in both experiments using a spatial cueing pa radigm. We observed no alterations in attentional facilitation toward spatial cu es suggesting that covert attentional orienting is not influenced by exercise fa tigue or caffeine supplementation. Response times were increased (impaired) afte r exercise and this deterioration was prevented by caffeine supplementation. In the resting experiment, response times across all conditions and cues were decre ased (improved) with caffeine. Covert spatial attention was not influenced by ca ffeine. Together, the results of these experiments suggest that covert attention al orienting is robust to the effects of fatiguing exercise and not influenced b y caffeine. However, exercise fatigue impairs response times, which can be preve nted by caffeine, suggesting that pre-motor planning and execution of the motor responses required for performance of the cueing task are sensitive to central n ervous system fatigue. Caffeine improves response time in both fatigued and fres h conditions, most likely through action on networks controlling motor function.