Long-term exposure to high altitude causes adaptive changes in several blood biochemical markers along with a marked body mass reduction involving both the lean and fat components. The aim of this study was to evaluate the impact of extended physical strain, due to extensive trekking at high altitude, on body composition, selected biomarkers in the blood, and the protective role of a high-protein diet in muscle dysfunction. We found that physical strain at high altitude caused a significant reduction in body mass and body fat, with a concomitant increase in the cross-sectional area of thigh muscles and an unchanged total lean body mass. Further, we found reductions in plasma leptin and homocysteine, while myoglobin, insulin, and C-reactive protein significantly increased. Creatine kinase, lactate dehydrogenase, and leptin normalized per body fat were unchanged. These findings demonstrate that high-altitude hypoxia, involving extended physical effort, has an impact on muscle function and body composition, facilitating sarcopenia and affecting body mass and fat distribution. It also activates pro-inflammatory metabolic pathways in response to muscular distress. These changes can be mitigated by a provision of a high-protein diet.