Based on the analysis of published data, it was shown that metabolic acidosis is an attribute of many extreme physiological and pathological conditions. It was found that metabolic acidosis is the main factor responsible for the fatigue and performance limitations during intense physical activities. According to prevailing views, metabolic acidosis during intense physical exertion is caused by the activation of glycolysis is due to insufficient activity of oxygen-dependent energy supply. However, the development and the degree of acidosis depend on whether the energy source that produces ATP consumes protons or release protons. Theoretical analysis of the published data that was performed in the study suggests that the cause of the acidosis is not the accumulation of insufficiently oxidized intermediate metabolites such as lactate and pyruvate, but hydrolysis of the ATP molecules, the resynthesis of which is not offset by oxidative phosphorylation.