This study compared the immune and stress response of oral contraceptive users (WomenOC; n = 9) to normally-menstruating women (WomenNM; n = 9) at rest and during exercise in temperate (TEMP; 22°C) and hot (HEAT; 35°C) conditions. Participants performed a 3-stage cycling trial in each condition at 90% (Stage 1; 30 min), 135% (Stage 2; 15 min), and 180% (Stage 3; 7.5 min) of lactate threshold 1. C-reactive protein (CRP) and immune cell counts were measured at rest, and serum cytokines (IL-1β, IL-1RA, IL-6, IL-8, IL-10, and TNF-α) and salivary cortisol were evaluated before and after exercise in both the TEMP and HEAT conditions. There were no differences in resting immune cell counts between groups, nor any differences in cortisol or any of the pro- or anti-inflammatory cytokines measured at rest or after completion of the exercise trials (p > 0.05). However, a trend for a higher resting CRP concentration was observed in WomenOC relative to WomenNM (1.102 ± 1.182 and 0.326 ± 0.228, respectively, p = 0.07). The results obtained in the current study indicate similar immunoendocrine function in WomenOC and WomenNM both at rest and after exercise in temperate and hot environments.

• No previous study has investigated the combined effect of heat and exercise on the immune response of women taking oral contraceptives

• Resting C-reactive protein was more than three times higher in the women taking the active oral contraceptive pills compared to naturally menstruating women during the early follicular phase

• There were no differences in resting immune cell counts between groups, nor any differences in cortisol or any of the pro- or anti-inflammatory cytokines measured at rest or after completion of the exercise trials

• With the exception of C-reactive protein, women using oral contraceptives exhibit similar immunoendocrine function to naturally menstruating women both at rest and after exercise in temperate and hot environments