ABSTRACT Passively elevating body temperature can trigger a potentially beneficial acute inflammatory response. However, heat therapy often causes discomfort and negative thermal perceptions, particularly in females who generally have lower heat tolerance than males. This study aimed to evaluate the impact of facial cooling on thermal comfort and interleukin-6 concentration in response to 60 minutes of dry heat exposure, and to investigate sex differences in physiological responses and perceptions. 22 healthy young adults (10 females, 12 males; age: 24.4 ± 3.3 years) completed three trials in randomized order using a dry sauna device: 1) Hyperthermia (71.1 ± 1.9°C; HEAT), 2) Hyperthermia with facial cooling via fans (71.1 ± 3.0°C; FAN), and 3) Normothermia (27.0 ± 0.9°C; CON). Blood samples to determine interleukin-6 (IL-6) plasma concentration were collected before and after exposure; basic affect and thermal comfort, rectal and skin temperature were assessed throughout the intervention. Rectal temperature following HEAT (38.0 ± 0.3°C) and FAN (37.8 ± 0.3°C) did not differ between males and females (p = 0.57). Females had higher forehead skin temperatures than males (p ≤ 0.019). Thermal comfort remained more positive in FAN compared to HEAT (p ≤ 0.002). Females felt more thermal discomfort than males in HEAT (p ≤ 0.03), but not in FAN (p = 0.28). The increase in IL-6 plasma concentration was similar between HEAT and FAN (p = 1.00), and higher than CON (p ≤ 0.02); there was no difference between males and females (p = 0.69). This study showed that facial cooling alleviated the thermal discomfort during heat exposure, particularly benefitted females, and did not impede the acute IL-6 response.