Abstract: Objective: To identify potential key metabolites alleviating sepsis-associated acute kidney injury(SAAKI) based on metabolomics, and to investigate the renal protective effect of glycoursodeoxycholic acid(GUDCA). Methods: From July 2024 to February 2025, 60 sepsis patients admitted to the intensive care unit(ICU) of Bobai County People's Hospital in Guangxi were selected and divided into AKI group(n=30) and control group(n=30) based on the presence or absence of acute kidney injury(AKI). Spearman correlation analysis was used to explore the correlation of bile acid metabolites with kidney function and prognosis-related indicators. Male C57 BL/6 mice were divided into control group, GUDCA group, lipopolysaccharide(LPS) group and GUDCA+LPS group. A mouse model of SA-AKI was established via intraperitoneal injection of LPS. Plasma urea nitrogen levels were detected using the diacetyl-monoxime colorimetric method. Plasma creatinine levels were measured using the creatine oxidase method. Plasma levels of inflammatory factors interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α(TNF-α) were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe pathological changes in kidney tissues. Immunofluorescence staining was used to detect the expressions of kidney injury markers neutrophil gelatinase-associated lipocalin(NGAL) and kidney injury molecule-1(KIM-1), and quantitative real-time polymerase chain reaction(RTqPCR) was used to detect the expressions of oxidative stress-related genes in kidney tissues. An LPS-induced human renal tubular epithelial cell injury model was established, and the levels of reactive oxygen species(ROS) and the expressions of inflammatory factors were detected after the intervention with GUDCA. Results: GUDCA was negatively correlated with plasma creatinine level and positively correlated with glomerular filtration rate(GFR), 24-hour urine output, and 28-day survival rate(P<0.05). Compared with those in the control group, mice in the LPS group exhibited aggravated renal tubular pathological damage, increased fluorescence intensities of KIM-1 and NGAL, increased plasma creatinine, urea nitrogen, IL-1 β, IL-6 and TNF-α levels and relative expressions of NOX4 gene in kidney tissues, and decreased relative expressions of SOD2 and GPX1 genes(P<0.05). Compared with those in the LPS group, mice in the GUDCA+LPS group showed alleviated renal tubular pathological damage, decreased fluorescence intensities of KIM-1 and NGAL, decreased plasma creatinine, urea nitrogen, IL-1 β, IL-6 and TNF-α levels and relative expressions of NOX4 gene in kidney tissues, increased relative expressions of SOD2 and GPX1 genes and increased expressions of NQO1, HO-1 and Nrf2(P<0.05). Cell experiments demonstrated that compared with the control group, the LPS group exhibited increased levels of ROS and expressions of IL-1β、IL-6 and TNF-α in HK-2 cells(P<0.05), whereas compared with the LPS group, the GUDCA+LPS group showed decreased levels of ROS and expressions of IL-1β、IL-6 and TNF-α in HK-2 cells after the intervention with GUDCA(P<0.01). Conclusion: GUDCA is correlated with the degree of renal function impairment and short-term prognosis in SA-AKI. It can alleviate renal tubular injury by inhibiting inflammatory response and oxidative stress, suggesting its potential as a biomarker for SA-AKI.