Sepsis‑associated encephalopathy (SAE) is a severe diffuse brain dysfunction in patients with sepsis. The mitochondria are an important site of energy metabolism, and mitochondrial structural changes and dysfunction are closely related to the occurrence of SAE. This paper mainly discusses the possible pathogenesis of the mitochondria in SAE, and summarizes the maintenance of mitochondrial dynamic homeostasis, improvement of mitochondrial energy metabolism, inhibition of mitochondrial oxidative stress, reduction of mitochondrial damage‑mediated apoptosis, and regulation of mitochondrial autophagy, in order to provide new ideas for the treatment of SAE. In addition, severe and critical Coronavirus Disease 2019 (COVID‑19) can be complicated by sepsis. The mitochondria may serve as a new target for the treatment of COVID‑19 complicated by SAE.