Generation of reactive oxygen species (ROS) increase during altitude exercise. ROS are neutralized by antioxidant defense systems consisting of several enzymes and non-enzymatic compounds among which, alpha-tocopherol, vitamins A, beta-carotene and lycopene play important roles. An imbalance between the oxidants and anti-oxidants can cause oxidative damages to cells and tissues. Several biomarkers are available to quantify the oxidatively-modified macromolecules. The assessment of malondialdehyde (MDA) and protein carbonyl content (PCC) are widely employed assays used to determine lipid peroxidation and oxidative damage to proteins, respectively. Since the ROS removal rate is mostly controlled by low molecular weight antioxidants, interest is growing in determining the total antioxidant status (TAS). We investigated the effect of a 43-days expedition ranging from 0 to 5900m on serum antioxidant defense system in 7 climbers (MANASLU 2008). TAS, PCC, MDA, lycopene and antioxidant vitamins concentrations were measured in serum before and immediately after expedition. No significant effects were observed in any parameters. Pre-expedition BMI and TAS were inversely correlated and the same correlation was demonstrated between TAS and fat mass. These correlations were lost in post-expedition subjects. Vit A and E expedition-induced variations were also positively associated. A progressively adaptive physical exercise in high altitude environment seem not to show a severe impact on the antioxidant-related biochemical human profile. Our results seem to indicate body mass and, in particular, fat mass percentage as possible factors involved in the antioxidant defense performance.