A new study published inFrontiers in Medicinerevealed a strong link between autoimmune diseases (AID) and the prevalence of delirium in the ICU, highlighting the necessity of increased delirium monitoring and prompt treatment for AID patients. Delirium, marked by disruptions in awareness, attention, and cognition, is a common sign of acute brain malfunction. In the context of mental health, it is seen as a temporary but severe cognitive and behavioral problem. Thus, this study assessed the relationship between autoimmune disorders and the prevalence of delirium in ICU patients. This research found patients with recorded delirium assessments and first ICU admissions using the eICU Collaborative Research Database. The patients were divided AID and non-AID. Key baseline factors, including demographics, comorbidities, therapeutic therapies, and severity levels, were balanced using inverse probability weighting (IPTW) and propensity score matching (PSM). The emergence of delirium was the main result. Using Cox proportional hazards and competing risk models, the relationship between AID and the incidence of ICU delirium was examined. Sensitivity and subgroup analyses were used to gauge the stability of the findings. Of the 8,978 patients, 29.7% had delirium (1,007 with AID and 7,971 without). In univariate and multivariable Cox analyses, AID was substantially linked to an elevated risk of delirium in both crude and matched populations (p < 0.001). After controlling for competing risks of in-ICU mortality, the Fine and Gray models indicated a greater frequency of delirium in the AID group (p < 0.001). The two groups' ICU mortality rates do not differ significantly, according to the KM curves. Overall, the therapeutic significance of identifying immunological disease status in delirium care is highlighted in this study, which is the first extensive data showing a substantial correlation between AID and ICU delirium. This work not only demonstrates the molecular connection between inflammation-immune dysregulation and neurological impairment, but it also validates AID as an independent risk factor for ICU delirium by a methodical comparison of these findings with existing studies. Huang, S.-T., Yu, K.-H., Yuan, J.-W., Sun, Y.-B., Huang, Z.-Y., & Liu, L.-P. (2025). The impact of autoimmune diseases on delirium risk in critically ill patients: a propensity score matching multicenter analysis. Frontiers in Medicine, 12, 1621441.https://doi.org/10.3389/fmed.2025.1621441