Sepsis-associated encephalopathy (SAE) is a diffuse and acute cerebral dysfunction caused by sepsis. Many sepsis patients exhibit acute deterioration in mental status during the early stage of disease, and central nervous system dysfunction has been shown to increase patient mortality. The present study selected 284 sepsis patients who were admitted to the Intensive Care Unit of Beijing Friendship Hospital, Capital Medical University, from January to December 2009. The patients were assigned to SAE and non-SAE patient groups according to SAE occurrence. SAE incidence was 37.68%, and mortality was significantly greater in SAE patients compared with non-SAE patients (41.12% vs. 17.51%, P < 0.01). Univariate analysis and multivariate logistic regression analysis indicated lower arterial partial pressure of oxygen and greater alanine aminotransferase and Acute Physiology and Chronic Health Evaluation II scores in the SAE group compared with the non-SAE group. Arterial partial pressure of oxygen, alanine aminotransferase, and Acute Physiology and Chronic Health Evaluation II scores were determined to be potential risk factors for SAE.