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It has been suggested that improper post-exercise recovery or improper sequence of training may result in an ‘accumulation’ of fatigue. Despite this suggestion, there is a lack of clarity regarding which physiological mechanisms may be proposed to contribute to fatigue accumulation. The present paper explores the time course of the changes in various fatigue-related measures in order to understand how they may accumulate or lessen over time following an exercise bout or in the context of an exercise program. Regarding peripheral fatigue, the depletion of energy substrates and accumulation of metabolic byproducts has been demonstrated to occur following an acute bout of resistance training; however, peripheral accumulation and depletion appear unlikely candidates to accumulate over time. A number of mechanisms may contribute to the development of central fatigue, postulating the need for …