Comparative studies on the adaptation pattern of antioxidant status among high altitude natives and acclimatized sojourners are very scanty. The aim of the present study was to compare the differences in antioxidant profile between two groups of active male volunteers, i.e. native highlanders (HAN, n=66) in their natural hypoxic environment with that of sojourners (SOJ, n=81) from sea level (SL) after 4 weeks of stay at an altitude of 4560m. Blood samples of SOJ were collected at SL and HA. Same was collected from HAN once at HA. HAN had significantly higher SOD activity and significantly lower catalase, GPX and GR activities than SOJ at HA. Ratio of GSH/GSSG was also significantly higher in HAN than SOJ at HA. In SOJ, antioxidant profile showed an upregulation after HA stay but it was not effective to reduce the levels of oxidative stress markers. Therefore, it can be stated that lifelong exposure to hypoxia has beneficial adaptive effects on antioxidant system in HAN. Similarly, acclimatization to HA also has beneficial preconditioning effects on antioxidant system in SOJ, but, may not be sufficient to ameliorate oxidative stress completely. Transient increase in metabolic rate due to hypoxia may be a causative factor for excess free radical generation among sojourners at HA.