The main objective of my current research project is to investigate sex-based differences in diaphragmatic fatigue (DF) after a pressure-threshold loading protocol under normoxic, acute hypoxic and hyperoxic conditions. In addition, to verify if there is a correlation between the magnitude of diaphragmatic fatigue, work of breathing, and oxygen availability. It is well acknowledged that women have smaller airways relative to lung size compared to men; this predisposes women to greater mechanical constraints during respiratory high-demand activities (i.e. exercise). For example, compared to men, women are more likely to develop exercise-induced arterial hypoxemia, have greater end-expiratory lung volume and for a given ventilation, and have a higher work of breathing. What’s more, previous studies demonstrated that the disparity in total work of breathing between men and women could be explained by women possessing a substantially larger resistive work of breathing (inspiratory and expiratory), which could be due to their smaller airways. Additionally, it is known that during exercise under hypoxia, there is an increase in ventilation, circulating metabolites, and WOB, while a decrease in O2 transport to the diaphragm also takes place. Thus, in the face of reduced O2 availability, the system shifts its energy generation substrate to use a higher percent of glycolytic pathways, hastening fatigue development. However, if those factors inherent to exercise were withdrawn, how would hypoxia influences DF? To date and the best of our knowledge, no study has investigated sex-based differences in DF under different O2 availabilities in the absence of whole-body exercise.