Hepcidin is a novel factor for iron deficiency in athletes, which is suggested to be regulated by interleukin-6 (IL-6) or erythropoietin (EPO). Purpose The purpose of the present study was to compare endurance exercise-induced hepcidin elevation among "normoxia", "hypoxia" and "combined heat and hypoxia". Methods Twelve males (21.5 +/- 0.3 years, 168.1 +/- 1.2 cm, 63.6 +/- 2.0 kg) participated in the present study. They performed 60 min of cycling at 60% of V & x2d9;O2max in either "heat and hypoxia" (HHYP; FiO2 14.5%, 32 degrees C), "hypoxia" (HYP; FiO2 14.5%, 23 degrees C) or "normoxia" (NOR; FiO2 20.9%, 23 degrees C). After completing the exercise, participants remained in the prescribed conditions for 3 h post-exercise. Blood samples were collected before, immediately and 3 h after exercise. Results Plasma IL-6 level significantly increased immediately after exercise (P < 0.05), with no significant difference among the trials. A significant elevation in serum EPO was observed 3 h after exercise in hypoxic trials (HHYP and HYP, P < 0.05), with no significant difference between HHYP and HYP. Serum hepcidin level increased 3 h after exercise in all trials (NOR, before 18.3 +/- 3.9 and post180 31.2 +/- 6.3 ng/mL; HYP, before 13.5 +/- 2.5 and post180 23.3 +/- 3.6 ng/mL, HHYP; before 15.8 +/- 3.3 and post180 31.4 +/- 5.3 ng/mL, P < 0.05). However, there was no significant difference among the trials during post-exercise. Conclusion Endurance exercise in "combined heat and hypoxia" did not exacerbate exercise-induced hepcidin elevation compared with the same exercise in "hypoxia" or "normoxia".