Objective To explore the relationship between serum long non-coding RNA X-inactive specific transcript(LncRNA XIST)and microRNA-122-5p(miR-122-5p)expression and the severity of brain injury and prognosis in patients with sepsis-associated encephalopathy(SAE).Methods A total of 108 SAE patients(SAE group)and 52 patients with sepsis only(non-SAE group)admitted to the Ankang Hospital of Tradi-tional Chinese Medicine from January 2019 to December 2023 were selected as the study subjects.According to the degree of brain injury,the SAE patients were categorized into mild brain injury group[Glasgow Coma Scale(GCS)score 13-14,27 cases],moderate brain injury group(GCS score 9-12,36 cases),and severe brain injury group(GCS score 3-8,45 cases).Based on the 28-day prognosis,they were divided into death group(51 cases)and survival group(57 cases).Serum LncRNA XIST and miR-122-5p expression levels were measured using real-time quantitative PCR.The binding site of LncRNA XIST and miR-122-5p was predicted using the StarBase database,and Pearson correlation analysis was performed to evaluate the relationship be-tween serum LncRNA XIST and miR-122-5p expression in SAE patients.Multivariate unconditional Logistic regression was used to determine the association between serum LncRNA XIST,miR-122-5p expression,and prognosis in SAE patients.Receiver operating characteristic curves were used to assess the predictive efficacy of LncRNA XIST and miR-122-5p expression for SAE prognosis.Results Compared with non-SAE group,se-rum LncRNA XIST expression was increased and miR-122-5p expression was decreased in SAE group,with statistical significance(P＜0.05).There were binding sites between LncRNA XIST and miR-122-5p,and the expression of LncRNA XIST in serum of SAE patients was negatively correlated with that of miR-122-5p(P＜0.05).Serum LncRNA XIST expression in mild brain injury group,middle brain injury group and severe brain injury group was increased successively,while miR-122-5p expression was decreased successively,with statistical significance(P＜0.05).The 28-day mortality rate of SAE patients after admission was 47.22％(51/108).Compared with the survival group,the expression of serum LncRNA XIST was higher in the death group,and the expression of miR-122-5p was lower,with statistical significance(P＜0.05).High sequential organ failure assessment(SOFA)score and high expression of LncRNA XIST were independent risk factors for death in SAE patients,while high GCS scores and high miR-122-5p expression of were independent protec-tive factors(P＜0.05).The combined expression of serum LncRNA XIST and miR-122-5p predicted the death of SAE patients with greater area under the curve than that of serum LncRNA XIST and miR-122-5p a-lone(P＜0.05).Conclusion Elevated serum LncRNA XIST and decreased miR-122-5p expression levels are associated with the severity of brain injury and poor prognosis in SAE patients.The combined detection of Ln-cRNA XIST and miR-122-5p has a high predictive value for SAE prognosis.