Loss of body mass and exercise intolerance are common findings in chronic obstructive pulmonary disease and are often difficult to reverse despite optimal nutritional intake. Similar findings have been reported in healthy individuals during high-altitude exposure. The role of hypoxia in modulating metabolism has been largely investigated in vitro and in animal studies. More fragmentary is the knowledge regarding hypoxia effects on in-vivo human metabolism. This paper reviews recent literature regarding the effects of chronic exposure to hypoxia on metabolism, particularly comparing chronic obstructive pulmonary disease patients with humans exposed to high altitude.