Obesity is nowadays a major public health problem. The World Health Organization reported that globally 400 million adults are obese, and the situation seems to raise in the future. Furthermore, obesity is a major risk factor for a number of chronic diseases such as type 2 diabetes, cardiovascular diseases and the metabolic syndrome. Interestingly, several studies have reported that appetite suppression and body weight loss are frequently observed at high altitude. This observation has opened some possibilities for losing weight under hypoxia or living in altitude. Nevertheless, the triggering mechanisms for the decrease in energy intake in hypoxic conditions still remain unclear as well as the impact on body mass components. On the other hand, obese subjects often present a chronic inflammatory state on the adipose tissue that might have a strong relationship with onset and development of obesity-related diseases. Thus, it has been consistently reported that adipose tissue of obese subjects is poorly oxygenated and that this hypoxia state is a new potential risk factor for the chronic inflammation in obesity. In this sense, oxygen therapy is a common technique used in current medicine for the treatment of several diseases, while animal studies have demonstrated that treatment with hyperoxia produces some beneficial effects in different diseases related with lack of oxygen in several organs. In this article, we review the role of oxygen availability in body weight homeostasis and hypothesize the possible applicability of hypoxia and hyperoxia for the treatment of obesity and related disorders.