Abstract: Objective:To investigate whether mild hypothermia could inhibit ferroptosis in mice with sepsis-as-sociated acute kidney injury (S-AKI) by activating NF-E2-related factor 2 (Nrf2), thus playing a protective role.Methods:15 SPF C57BL/6 mice were randomly divided into sham operation group(group S), sepsis normal tem-perature group(group N)and sepsis mild hypothermia group(group H), with 5 mice in each group.Cecal ligation and puncture was used to establish a mouse model of sepsis and corresponding treatment was carried out in the three groups.Hematoxylin-eosin (HE) staining was used to observe the damage of kidney tissue.The levels of urea nitrogen (BUN) and creatinine (Cr) in serum, the contents of reduced glutathione (GSH) and malondialde-hyde (MDA) in kidney tissue were determined by enzyme-labeled assay.Western blotting and real-time fluores-cence quantitative polymerase chain reaction (RT-qPCR) were used to determine the protein and mRNA expres-sion levels of acyl CoA synthetase long chain family member 4(ACSL4), glutathione peroxidase 4(GPX4), Nrf2 and its downstream factor heme oxygenase 1 (HO-1) in kidney tissue.Results:Compared with group S, there were different degrees in the pathological changes of kidney tissue in N and H groups, the levels of BUN and Cr in serum increased, GSH content decreased, MDA content increased, the expression of ACSL4 protein and mRNA increased, the expression of GPX4 protein and mRNA decreased, and the expressions of NRF2 and HO-1 protein and mRNA significantly increased(all P< 0.05).Compared with group N, group H showed reduced path-ological damage, decreased levels of BUN and Cr, increased GSH content, decreased MDA content, de-creased expression of ACSL4 protein and mRNA, increased expression of GPX4 protein and mRNA, and signifi-cantly increased expressions of Nrf2 and HO-1 protein and mRNA(all P< 0.05).Conclusion:Mild hypothermia can inhibit ferroptosis by activating Nrf2 and play a protective role in S-AKI.