Background: The immune system is influenced by many factors such as physical activity. The aim of this study was to examine the effects of intermittent severe exercise in hypoxia and normoxia on proinflammatory cytokines (IL-6, TNF-α, IL-1β) in response to exhaustive exercise. Materials and methods: Totally, 16 male active (age 23.27±2.94years) were randomly divided into two groups: activity in hypoxic conditions (%14O2) and normoxia (%21O2). Maximum workload (Wmax) was determined before training for all participants. The same exhaustive tests were carried out before and after the exercise, which blood samples were taken before and immediately after exhaustive tests. The training protocol consisted of 40min of exercise, 6 days per week, for 2 weeks, which included a 5min warm up, 10 steps of 3min pedaling (one minute with an intensity of 80-85% Wmax, and two minutes at 50% Wmax), and 5min cool down. The first group training was performed in in hypoxic conditions and the second group was in noemoxia. For data analysis repeated-measures analysis of variance was used. Results: The results showed that exercise in hypoxic conditions resulted in a significant increase in IL-6 (p=0.002) than of the normoxia, but no significant difference in the IL-1β (p=0.078) and TNF-α (p=0.072) was observed. Conclusion: Based on the results of the present study, periodic extreme exercise in hypoxic conditions could modify cytokines and increase the levels of IL-6.