Purpose: This study evaluates the effect of hyperoxia on cerebral oxygenation and neuromuscular fatigue mechanisms of the elbow flexor muscles following ergometer rowing. Methods: In 11 competitive male rowers (age, 30 ± 4 years), we measured near-infrared spectroscopy determined frontal lobe oxygenation (ScO₂) and transcranial Doppler ultrasound determined middle cerebral artery mean flow velocity (MCA V_mean) combined with maximal voluntary force (MVC), peak resting twitch force (P_tw) and cortical voluntary activation (VA_TMS) of the elbow flexor muscles using electrical motor point and magnetic motor cortex stimulation, respectively, before, during, and immediately after 2,000 m all-out effort on rowing ergometer with normoxia and hyperoxia (30% O₂). Results: Arterial hemoglobin O₂ saturation was reduced to 92.5 ± 0.2% during exercise with normoxia but maintained at 98.9 ± 0.2% with hyperoxia. The MCA V_mean increased by 38% (p < 0.05) with hyperoxia, while only marginally increased with normoxia. Similarly, ScO₂ was not affected with hyperoxia but decreased by 7.0 ± 4.8% from rest (p = 0.04) with normoxia. The MVC and P_tw were reduced (7 ± 3% and 31 ± 9%, respectively, p = 0.014), while VA_TMS was not affected by the rowing effort in normoxia. With hyperoxia, the deficit in MVC and P_tw was attenuated, while VA_TMS was unchanged. Conclusion: These data indicate that even though hyperoxia restores frontal lobe oxygenation the resultant attenuation of arm muscle fatigue following maximal rowing is peripherally rather than centrally mediated.