Based on previous observations in hyperbaric hyperoxia, we hypothesized that normobaric hyperoxia, often used during general anaesthesia and resuscitation, might also induce a neuromuscular excitability. In healthy volunteers, we studied the consequences of a 50 min period of pure oxygen breathing on the neuromuscular conduction time (CT), the amplitude of the compound evoked muscle potential (M-wave), the latency and amplitude of the Hoffman reflex (H reflex) and the electromyographic tonic vibratory response (TVR) of the flexor digitorum superficialis muscle to explore the proprioceptive reflex loop. Hyperoxia-induced oxidative stress was measured by the changes in blood markers of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant response (reduced ascorbic acid, RAA). During hyperoxia, the M-wave amplitude increased, both CT and H reflex latency were shortened, and the H reflex amplitude increased. By contrast, TVR significantly decreased. Concomitantly, an oxidative stress was assessed by increased TBARS and decreased RAA levels. This study shows the existence of dual effects of hyperoxia, which facilitates the muscle membrane excitability, nerve conduction and spinal reflexes, but reduces the gain of the proprioceptive reflex loop. The activation of the group IV muscle afferents by hyperoxia and the resulting oxidative stress might explain the TVR depression.