Objective: To investigate the clinical significance of transcranial Doppler (TCD) in early diagnosis of sepsis-associated encephalopathy(SAE). Methods: Septic patients admitted to the intensive care unit(ICU) were recruited at Xiangya Hospital, Central South University from July 2015 to March 2016. Clinical data and TCD parameters during 24 hours after admission were collected. All patients were screened for delirium using the confusion assessment method for the intensive care unit (CAM-ICU) twice a day. The gold standard of the diagnosis of SAE was positive CAM-ICU evaluation. Patients were divided into SAE group and the non-SAE group. TCD data including systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), pulsatility index (PI) and resistant index (RI) were analyzed to determine the optimal diagnostic cut-off value. Results: A total of 43 patients were enrolled including 12 in SAE group and 31 in non-SAE group. Vm and Vd were lower in SAE group [Vm: (53.50±12.22) cm/s vs. (61.68±9.63) cm/s, P<0.05; Vd: (33.42±10.87) cm/s vs. (43.16±7.84) cm/s, P<0.01] but PI and RI were significant higher in SAE group[PI:(1.16±0.2) vs. (0.90±0.15), P<0.01;RI:(0.65±0.08) vs. (0.56±0.06), P<0.01] than in non-SAE group. The cut-off values of Vs, Vm, Vd, PI and RI for the diagnosis of SAE were 112cm/s, 55.50cm/s, 34.50cm/s, 1.16, 0.65, respectively, with the relevant sensitivities of 19.4%, 83.9%, 93.5%, 58.3%, 58.3% and the specificities of 100.0%, 50.0%, 58.3%, 96.8%, 96.8%, respectively. The diagnostic AUC of Vd, PI and RI were 0.741, 0.808 and 0.808 respectively. Conclusions The parameter changes of TCD suggest that the pathogenesis of SAE is related to cerebral hypoperfusion, TCD is a helpful method for the early diagnosis of SAE.