Clinical features of sepsis-associated encephalopathy in children with different prognoses were analyzed and the changes of regional cerebral oxygen saturation (rScO
2
) and central venous oxygen saturation (ScvO
2
) were measured. Eighty children with sepsis-related encephalopathy, admitted to the Pediatric Intensive Care Unit (PICU) of the Children's Hospital Affiliated to Zhengzhou University, were enrolled in this study and post-intensive care syndrome (PICS) scoring was performed within 24 h after admission. Patients were separated into groups according to the score results and treatment outcomes. Clinical features, functional tests, imaging examinations, PICS scores, and modified Glasgow Coma Scale (GCS) scores were compared among children with varying severities and prognoses. The changes of rScO
2
and ScvO
2
at different time-points among children with different prognoses were measured and compared. According to PICS scores, there were 8 non-critically ill children, 42 critically ill children, and 30 extremely critically ill children. Fifty-two children survived, and the survival rate was 65%. Comparison of the clinical characteristics of children with different conditions showed that deep coma, generalized seizure, severe electroencephalogram (EEG) abnormalities, and the survival of children were significantly associated with the severity of disease (P<0.05). At the same time, compared to the survivors group, the rates of generalized seizures and severe EEG abnormalities were significantly increased in the deceased children group, while the PICS and GCS scores were significantly decreased (P<0.05). rScO
2
values in the deceased group were lower than those in the survival group at different time-points, but the differences were not significant (P>0.05). On the contrary, ScvO
2
values were significantly higher in the deceased group than those in the survivors group (P<0.05). The lower the PICS and GCS scores in children with sepsis-related encephalopathy, the more serious the condition, and the more likely to develop disturbance of consciousness, epileptic seizures, and abnormal EEG changes. Whereas, changes of ScvO
2
are closely related to prognosis.