PURPOSE: Exercise-induced central fatigue is alleviated following acclimatisation to high altitude. The adaptations underpinning this effect may also be induced with brief, repeated exposures to severe hypoxia. The purpose of this study was to determine whether (i) exercise tolerance in severe hypoxia would be improved following an intermittent hypoxic (IH) protocol and (ii) exercise-induced central fatigue would be alleviated following an IH protocol.METHODS: Nineteen recreationally-active males were randomised into two groups who completed ten 2-h exposures in severe hypoxia (IH: PIO2 82 mmHg; n=11) or normoxia (control; n=8). Seven sessions involved cycling for 30 min at 25% peak power (W˙peak) in IH, and at a matched heart rate in normoxia. Participants performed baseline constant-power cycling to task failure in severe hypoxia (TTF-Pre). After the intervention, the cycling trial was repeated (TTF-Post). Pre- and post-exercise, responses to transcranial magnetic stimulation and supramaximal femoral nerve stimulation were obtained to assess central and peripheral contributions to neuromuscular fatigue.RESULTS: From pre- to post-exercise in TTF-Pre, maximal voluntary force (MVC), cortical voluntary activation (VATMS) and potentiated twitch force (Qtw,pot) decreased in both groups (all p < 0.05). Following IH, TTF-Post was improved (535 ± 213 s vs. 713 ± 271 s, p < 0.05) and an additional isotime trial was performed. After the IH intervention only, the reduction in MVC and VATMS was attenuated at isotime (p < 0.05). No differences were observed in the control group.CONCLUSION: Whole-body exercise tolerance in severe hypoxia was prolonged following a protocol of IH. This may be related to an alleviation of the central contribution to neuromuscular fatigue.