Obstructive sleep apnoea (OSA) is characterized by recurrent collapse of the upper airway during sleep, subjecting the patient to recurrent bouts of intermittent hypoxia. Chronic intermittent hypoxia (CIH) has been shown to induce upper airway muscle dysfunction¹, perhaps via the production of reactive oxygen species². First, we examined the effect of hydrogen peroxide (H₂O₂) on contractile properties of the rat sternohyoid muscle at varying temperatures. Second, we investigated the effect of H₂O₂ in the presence of an iron chelator, deferoxamine (DFX) on skeletal muscle contraction. DFX prevents the generation of hydroxyl radicals from H₂O₂. Adult male Wistar rats were anaesthetized with 5% isoflurane and killed by spinal transection. Sternohyoid muscle strips were mounted isometrically in water-jacketed tissue baths at 27°C or 35°C and either bubbled with a hyperoxic (95% O₂/5% CO₂) or anoxic (95% N₂/5% CO₂) gas mixture. Studies were conducted under control conditions (no drug), in the presence of 1mM H₂O₂ or 1mM H₂O₂ plus 1mM DFX. Strips were set to optimal length and force-frequency relationship was assessed by stimulating the muscle every two minutes at 10, 20, 30, 40, 60, 80 and 100 Hz for 300ms. Fatigue was induced by repeated tetanic contractions (40Hz, 300ms duration) every 2 seconds for 2 minutes. At 27°C, H₂O₂ had no significant effect on muscle force under hyperoxic (22±3 vs. 17±2 N/cm², mean±SEM, control n=5 vs. H₂O₂ n=5 at 100 Hz, P>0.05, ANOVA) or hypoxic conditions. H₂O₂-treated muscle strips exhibited increased fatigue under hyperoxic conditions (63±3% vs. 39±3%, control n=6 vs. H₂O₂ n=6 at 2 min, P<0.05, ANOVA). Similar results were seen in hypoxia (63±7% vs. 25±2%, control n=7 vs. H₂O₂ n=5 at 2 min, P<0.05, ANOVA). At a more physiological temperature of 35°C, H₂O₂ again did not alter sternohyoid contractile force under hyperoxic or hypoxic conditions. Fatigue was increased in H₂O₂-treated muscle strips compared to control strips in hyperoxia (98±5% vs. 57± 9%, control n=6 vs. H₂O₂ n=7 at 2 min, P<0.05, ANOVA) and hypoxia (60±7% vs. 15±6%, control n=7 vs. H₂O₂ n=6 at 2 min, P<0.05, ANOVA). Co-incubation of H₂O₂ with DFX significantly improved the fatigue index of the muscle strips compared to H₂O₂ alone in hyperoxia (83±3% vs. 57± 9%, H₂O₂ plus DFX n=6 vs. H₂O₂ n=7 at 2 min P<0.05, ANOVA) but this improvement did not reach statistical significance in hypoxia. In summary, H₂O₂ increased fatigability of a pharyngeal dilator muscle but failed to show any effect on muscle force at both 27°C and 35°C. Muscle strips co-incubated with H₂O₂ and DFX showed a marked improvement in muscle endurance partially reversing the effects of H₂O₂ alone. DFX prevents the formation hydroxyl radicals from H₂O₂ and therefore the effects of H₂O₂ on muscle fatigue are presumably partially attributed to H₂O₂ itself and partially to an effect of hydroxyl radicals.