This study investigated the effects of acute hypoxia on spinal reflexes and soleus muscle function after a sustained contraction of the plantar flexors at 40% of maximal voluntary isometric contraction (MVC). Fifteen males (age 25.3 ± 0.9 year) performed the fatigue task at two different inspired O₂ fractions (FiO₂ = 0.21/0.11) in a randomized and single-blind fashion. Before, at task failure and after 6, 12 and 18 min of passive recovery, the Hoffman-reflex (H max) and M-wave (M max) were recorded at rest and voluntary activation (VA), surface electromyogram (RMSmax), M-wave (M sup) and V-wave (V sup) were recorded during MVC. Normalized H-reflex (H max/M max) was significantly depressed pre-exercise in hypoxia compared with normoxia (0.31 ± 0.08 and 0.36 ± 0.08, respectively, P < 0.05). Hypoxia did not affect time to task failure (mean time of 453.9 ± 32.0 s) and MVC decrease at task failure (-18% in normoxia vs. -16% in hypoxia). At task failure, VA (-8%), RMSmax/M sup (-11%), H max/M max (-27%) and V sup/M sup (-37%) decreased (P < 0.05), but with no FiO2 effect. H max/M max restored significantly throughout recovery in hypoxia but not in normoxia, while V sup/M sup restored significantly during recovery in normoxia but not in hypoxia (P < 0.05). Collectively, these findings indicate that central adaptations resulting from sustained submaximal fatiguing contraction were not different in hypoxia and normoxia at task failure. However, the FiO₂-induced differences in spinal loop properties pre-exercise and throughout recovery suggest possible specific mediation by the hypoxic-sensitive group III and IV muscle afferents, supraspinal regulation mechanisms being mainly involved in hypoxia while spinal ones may be predominant in normoxia.