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Sepsis-associated encephalopathy causes long-term health problems in patients with sepsis. This review ex-plores the pathogenesis of sepsis-associated encephalopathy, including its effects on the blood-brain barrier, microglia ac-tivation, mitochondrial dysfunction, the inflammatory medium and neurotransmitters and its roles in amino acid balance disorders, hyperammonemia, and intestinal flora imbalance. Understanding the etiology of sepsis-associated encephalopa-thy may allow the development of adjunctive therapies targeting its under