OBJECTIVE We explored the effect of heat stress during an acute endurance exercise session in hypoxia on endocrine and metabolic responses. METHODS A total of 12 healthy males cycled at a constant workload (60% of the power output associated with their maximal oxygen uptake under each respective condition) for 60 min in three different environments: exercise under hot and hypoxia (H+H; fraction of inspiratory oxygen or FiO2: 14.5%, 32°C), exercise under hypoxia (HYP; FiO2: 14.5%, 23°C), and exercise under normoxia (NOR; FiO2: 20.9%, 23°C). After completing the exercise, participants remained in the chamber for 3 h to evaluate metabolic and endocrine responses under each environment. Changes in muscle oxygenation (only during exercise), blood variables, arterial oxygen saturation, and muscle temperature were determined up to 3 h after exercise. RESULTS Serum erythropoietin (EPO) level was increased to similar levels in both H+H and HYP at 3 h after exercise compared with before exercise (P < 0.05), whereas no significant increase was found under NOR. No significant difference between H+H and HYP was observed in the serum EPO level, blood lactate level, or muscle oxygenation at any time (P > 0.05). Exercise-induced serum growth hormone (GH) elevation was significantly greater in H+H compared with HYP (P < 0.05) and HYP showed significantly lower value than NOR (P < 0.05). Arterial oxygen saturation during exercise was significantly lower in H+H and HYP compared with NOR (P < 0.05). Furthermore, H+H showed higher value compared with HYP (P < 0.05). CONCLUSIONS The serum EPO level increased significantly with endurance exercise in hypoxia. However, the addition of heat stress during endurance exercise in hypoxia did not augment the EPO response up to 3 h after completion of exercise. Exercise-induced GH elevation was significantly augmented when the hot exposure was combined during endurance exercise in hypoxia. Muscle oxygenation levels during endurance exercise did not differ significantly among the conditions. These findings suggest that combined hot and hypoxic stresses during endurance exercise caused some modifications of metabolic and endocrine regulations compared with the same exercise in hypoxia.