Sex differences exist in the integrative response to exercise, however, these are typically researched during constant-load exercise. Interval exercise involves high-intensity efforts interspersed with recovery periods to repeatedly stress physiological systems, and it is currently unknown whether the response to this form of exercise differs between sexes. Ten males and ten females (age: 25±3 years) completed two experimental visits. First, an incremental treadmill exercise test was performed to obtain submaximal (lactate threshold) and maximal ( O 2peak ) data. Thereafter, visit two involved 4 × 3-min running intervals at 90% of the final incremental test velocity (v O 2peak ), with 90 secs rest between intervals. Before exercise and after each interval, maximal voluntary contraction (MVC), quadriceps potentiated twitch (Q tw.pot ), and voluntary activation (VA) were recorded. The rates of oxygen uptake ( O 2 ), carbon dioxide production ( CO 2 ) and ventilation ( E ) were continuously recorded throughout. There was no sex difference in relative O 2peak (males: 47.2±6.0 vs. females: 44.4±5.8 ml.kg - 1. min -1 , p=0.292). When expressed relative to peak values, there were no sex differences in the O 2 or CO 2 response to the interval task (p≥0.781). Females had greater E , E / O 2 , and E / CO 2 values during the first two intervals (p≤0.046). There were no sex differences in the reductions in MVC, Q tw.pot , and VA during the interval task (p≥0.150), however females had lesser reductions in Q tw.pot values post-exercise (−24±9 vs. −15±8%, p=0.044). Sex differences exist in the physiological response to interval exercise. Compared to males, females experienced greater hyperpnoea during the initial stages, and had lesser decreases in contractile function post-exercise.