Brain dysfunction is a severe complication of sepsis with an incidence ranging from 9% to 71% that is associated with increased morbidity and mortality. Its diagnosis relies mainly on neurologic examination with clinical manifestations ranging from confusion to coma. An electroencephalogram, somatosensory evoked potentials, and measurement of plasma S-100b protein and neuron-specific enolase can be useful for the detection of brain dysfunction. Brain MRI can identify brain lesions such as cerebral infarction, posterior reversible encephalopathy syndrome, and leukoencephalopathy. The mechanism of sepsis-associated encephalopathy involves inflammatory and non-inflammatory processes that affect endothelial cells, glial cells, and neurons and induce blood-brain barrier breakdown, derangements of intracellular metabolism, and cell death. Specific treatments for sepsis-associated encephalopathy need to be developed. Currently, treatment is mainly the management of sepsis.