Wildland firefighters (WFF) face a set of specific work-related factors that directly affect their physical and cognitive abilities and compromise their health and safety. The working conditions include hard physical work and environmental conditions that combine high temperatures and high radiant heat. Such environments make using personal protective equipment (PPE) mandatory to protect them from risks. This fact restricts heat removal and adds extra weight, increasing thermal strain and the risk of heat-related illnesses on WFF. Since the number of females WFF has increased, it is necessary to study the repercussions of heat stress on this group. To date, it is not yet well-known whether sex-related differences in thermoregulation will be relevant when the individuals are wearing PPE and performing high physical effort in a hot environment. Therefore, we aimed to investigate the physiological response when performing moderate to high-intensity effort in a hot-dry environment while wearing PPE according to sex. Twenty WFF 10 females [23.9 ± 3.2 yr, 163.8 ± 3.4 cm and 62.7 ± 9.1 kg] and 10 males [31.9 ± 6.6 yr, 178.8 ± 5.8 cm and 73.9 ± 7.7 kg]) performed a 125 min treadmill test in a controlled ambient (30 ºC and 30% relative humidity). The protocol consisted of two exercise stages where WFF performed different continuous and variable exercise bouts in order to mimic the effort performed during real deployments. Participants wore the full standard PPE during the test. Oxygen uptake (VO2), heart rate (HR), core temperature (CT) and chest temperature (SkT) were monitored throughout the test. HR and CT were used to calculate the physiological strain index (PSI). Differences in body mass pre-post trials corrected for fluid intake were used to calculate sweat production (SwP), sweating rate (SwR), and evaporative efficiency (EE). Differences (p < 0.05) between females and males were found in %VO2max (62.5 ± 7.4 vs 55.3 ± 5.), HR (155 ± 10 vs 134 ± 14 beats·min–1), % of maximal HR (81.3 ± 3.5 vs 42.3 ± 6.5), CT (38.0 ± 10 vs 37.7 ± 0.33 ºC), SkT (36.0 ± 0.6 vs 35.3 ± 0.6 ºC) and PSI (4.1 ± 0.5 vs 3.5 ± 0.6). Even though SwR was higher (p < 0.05) for male participants (1001.5 ± 268.3 ml) compared to females (647.5 ± 145.9 ml), females had higher EE (32.9 ± 4.6 vs 16.7 ± 6.2 %). In conclusion, performing high-intensity exercise in hot-dry conditions while wearing PPE leads to a higher thermal and cardiovascular load for female WFF, making them more susceptible to heat illness. These results could be linked to lower aerobic fitness, sweating rate, and hormonal aspects that increased the thermal burden.