Research into sex differences in respiratory-related disorders such as chronic obstructive pulmonary disease and obstructive sleep apnoea syndrome suggest that differences at the level of the muscle are important (Skelly et al., 2010, Silverman et al., 2000). Hypoxia, a common feature of respiratory related diseases, has been observed to induce respiratory muscle dysfunction (Skelly et al., 2009) which is associated with deleterious clinical consequences such as dyspnoea, respiratory failure and premature death. We hypothesized that sex differences intrinsic to respiratory muscles will become apparent under hypoxic conditions. Male and female C57Bl6/J mice were humanely killed and diaphragm and sternohyoid (a representative upper airway dilator) muscle strips were excised. Isometric and isotonic contractile properties of muscle strips were examined in physiological solution at 35oC in vitro. Muscle strips were incubated in tissue baths under control (95%O2/5%CO2) or hypoxic (95%N2/5%CO2) conditions. All data was normalised to optimal length, or cross-sectional area as appropriate and was analysed using two-way ANOVA. Hypoxia alone, as expected, caused significant reductions in peak force, peak work and peak power in both muscles of both sexes. Sex alone, had no effect on peak work or peak power in either muscle group under control conditions. However female sternohyoid, but not diaphragm, peak force was significantly more tolerant under hypoxic conditions (Control v Hypoxia, mean ± SEM: 9.4±0.5N/cm2 v 4.3±0.61N/cm2 (male); 10.1±0.5N/cm2 v 8.0±0.7 N/cm2 (female); N= 6-7 per group). There was a significant sex-gas interaction (P=0.0143). There was a sex and a gas difference in diaphragm maximum shortening velocity (Lo/s=muscle lengths/second; Control v Hypoxia, mean ± SEM: 4.4±0.4Lo/s v 3.5±0.8Lo/s (male); 3.5±0.5Lo/s v 1.5±0.6Lo/s (female); N= 9,7,9,6 animals per group) but no interaction (P=0.3703). In contrast, neither sex nor gas had an effect on maximum shortening velocity in the sternohyoid (Control v Hypoxia, mean ± SEM: 5.5±0.8Lo/s v 7.5±1.3Lo/s; 5.4±0.5Lo/s v 5.1±0.8Lo/s; N= 6-7 animals per group) and there was no interaction (P=0.2172). We conclude that there are sex differences in hypoxic tolerance of murine upper airway dilator muscle. These differences potentially contribute to development, progression and outcomes of several respiratory related diseases.