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OBJECTIVE The purpose of the present study was to assess whether optic nerve sheath diameter (ONSD) measured by ultrasound could predict brain injury in sepsis associated encephalopathy (SAE). METHODS A total of 48 male New Zealand White rabbits were used to establish sepsis model. The levels of neuro-specific enolase (NSE), S100B, and myeloperoxidase (MPO) were detected by enzyme-linked immuno sorbent assay and ONSD were measured before modeling, 6hours, 12hours and 24hours after moldeling. Sixteen rabbits were sacrificed for hematoxylin-eosin (HE) staining of brain tissue and the brain water content at above time points. Rabbits demonstrated brain injury by HE staining were included in the SAE group, the others were enrolled in the control group. The correlation between ONSD and MPO, NSE and S100B in the SAE group were analyzed. Receiver operator characteristic curves were generated to analyze the area under the curve (AUC), specificity and sensitivity of ONSD values for SAE. RESULTS Twenty-nine of 48 rabbits had brain injury, while 19 cases were enrolled in the control group. The level of MPO, NSE, S100B at 6hours, 12hours and 24hours in SAE group were all higher than those of the control group with statistical significance. The ONSD in SAE group increased with time and significantly wider than those in the control group. Correlation analysis revealed that ONSD was positively correlated with MPO, NSE and S100B in the SAE group. The AUCs for the ONSD value in diagnosing SAE at 6h, 12h and 24h were 0.864, 0.957, 0.877, respectively. CONCLUSIONS Alterations in ONSD strongly correlated with MPO, NSE and S100B among SAE rabbits. Monitoring of ONSD exhibited a high predictive value for SAE. AVAILABILITY OF DATA AND MATERIAL The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.