Central fatigue refers to the central nervous system disease caused by excessive mental pressure or excessive physical activity, which shows a series of fatigue symptoms. The pathological mechanism of central fatigue remains unclear, and the mitochondrial quality control pathway represented by mitophagy is closely related to the occurrence and development of central fatigue. Traditional Chinese medicine considers liver stagnation and spleen deficiency as the key pathogenesis of central fatigue. This paper suggests that oxidative stress may be an important basis for the occurrence of central fatigue, energy metabolism disorders are specific manifestations of liver′s failure of conveyance and dispersion and spleen′s failure of healthy transportation, and the abnormal accumulation of reactive oxygen can be regarded as pathological products of central fatigue. Therefore, based on oxidative stress and energy metabolism, the pathologic mechanism of liver′s failure of conveyance and dispersion and spleen′s failure of healthy transportation in central fatigue from the perspective of mitophagy has a rich theoretical connotation, and provides a theoretical reference for the clinical treatment of central fatigue.