Purpose: Exercise-induced central fatigue is alleviated after acclimatization 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 after an intermittent hypoxic (IH) protocol and (ii) exercise-induced central fatigue would be alleviated after an IH protocol. Methods: Nineteen recreationally active men were randomized into two groups who completed ten 2-h exposures in severe hypoxia (IH: partial pressure of inspired O2 82 mm Hg; 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). Before and after 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 postexercise in TTF-Pre, maximal voluntary contraction (MVC), cortical voluntary activation (VATMS), and potentiated twitch force (Qtw,pot) decreased in both groups (all P
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