Intense inspiratory muscle work can evoke a metabolite stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26±4 y) males (n=9) and females (n=7) completed two experimental days. On day one participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA) and participants then completed isocapnic PTL to task failure. There was a significant sex and time interaction in the mean arterial pressure (MAP, p=0.015) and burst frequency (p=0.039) response to PTL. Males had a greater rise in MAP (∆ 21±9 mmHg) relative to females (∆ 13±5 mmHg, p=0.026). Males also demonstrated a greater rise in MSNA burst frequency (∆ 18±7 bursts/min) relative to females (∆ 10±5 bursts/min, p=0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (p=0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.