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Objective To systematically map the global and domestic research landscape of sepsis-associated encephalopathy (SAE) and to identify current hotspots and future trends. Methods Relevant articles published from 1 January 2000, to 1 August 2025 were retrieved from the Web of Science (WoS) Core Collection and the China National Knowledge Infrastructure (CNKI). Bibliometric software including CiteSpace V6.3. R1, VOSviewer V1.6.20 and Bibliometrix R V4.1.3 were employed to extract and visualize annual publications, distribution of research fields, countries/regions, authors, institutions, average citations per publication and keywords. Results A total of 1,097 articles were included in this study. Over the past 25 years, the annual articles and annual citations in the field of SAE have shown an overall upward trend. Among various sepsis-related organ complications, SAE has undergone rapid development and gained an increasingly prominent research status. Studies in this field are characterized by multidisciplinary integration, involving neuroscience, immunology, pharmacology and pharmacy, emergency medicine, neurology, and other disciplines. China ranks first in publication volume, followed by the United States and Brazil. Tianjin Medical University is the most productive institution, while Nanjing University holds the highest average citations per paper. Core research groups led by “Xie Keliang” and “Yang Jianjun” have been formed at home and abroad. Burst keyword analysis shows a shift from early mechanistic terms such as “nitric oxide synthase”, “cerebral blood flow” and “tumor necrosis factor” to recent intervention-oriented terms including “cells”, “inhibition”, “treatment” and “electroacupuncture”, indicating a transition from basic mechanism exploration to clinical application and targeted intervention. Conclusion SAE research continues to gain momentum. Future work should focus on the neuroinflammation-blood–brain barrier axis. Researchers may explore interactions among microglial activation, oxidative stress, and barrier damage, as well as the role of the vagal-immune metabolic pathway. Within a consensus-based framework, efforts can advance new prevention and treatment strategies. These strategies may combine multi-organelle targeted inhibition with multi-component interventions from traditional Chinese medicine (TCM).