Diaphragmatic fatigue occurs in highly trained athletes during exhaustive exercise. Since approximately half of them also exhibit exercise-induced arterial hypoxaemia (EIAH) during high-intensity exercise, the present study sought to test the hypothesis that arterial hypoxaemia contributes to exercise-induced diaphragmatic fatigue in this population. Ten cyclists (JOURNAL/jphy/04.02/00005245-200604150-00019/ENTITY_OV0312/v/2017-10-03T050438Z/r/image-pngO2max: 70.0 ± 1.6 ml kg−1 min−1; mean ±S.E.M.) completed, in a balanced ordering sequence, one normoxic (end-exercise arterial O2 saturation (Sa,O2): 92 ± 1%) and one hyperoxic (FI,O2: 0.5% O2; Sa,O2: 97 ± 1%) 5 min exercise test at intensities equal to 80 ± 3 and 90 ± 3% of maximal work rate (WRmax), respectively, producing the same tidal volume (VT) and breathing frequency (f) throughout exercise. Cervical magnetic stimulation was used to determine reduction in twitch transdiaphragmatic pressure (Pdi,tw) during recovery. Hyperoxic exercise at 90% WRmax induced significantly (P= 0.022) greater post-exercise reduction in Pdi,tw (15 ± 2%) than did normoxic exercise at 80% WRmax (9 ± 2%), despite the similar mean ventilation (123 ± 8 and 119 ± 8 l min−1, respectively), breathing pattern (VT: 2.53 ± 0.05 and 2.61 ± 0.05 l, f: 49 ± 2 and 46 ± 2 breaths min−1, respectively), mean changes in Pdi during exercise (37.1 ± 2.4 and 38.2 ± 2.8 cmH2O, respectively) and end-exercise arterial lactate (12.1 ± 1.4 and 10.8 ± 1.1 mmol l−1, respectively). The difference found in diaphragmatic fatigue between the hyperoxic (at higher leg work rate) and the normoxic (at lower leg work rate) tests suggests that neither EIAH nor lactic acidosis per se are likely predominant causative factors in diaphragmatic fatigue in this population, at least at the level of Sa,O2 tested. Rather, this result leads us to hypothesize that blood flow competition with the legs is an important contributor to diaphragmatic fatigue in heavy exercise, assuming that higher leg work required greater leg blood flow.