BACKGROUND: Sepsis, characterized by high morbidity and mortality, necessitates the identification of novel diagnostic and prognostic biomarkers to enhance patient outcomes. Prior research has highlighted the potential clinical utility of long non-coding RNAs (lncRNAs) in sepsis. This study aimed to investigate the clinical significance and underlying mechanisms of serum lncRNA Cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in sepsis. METHODS: Differentially expressed lncRNAs in sepsis patients were explored via GEO database. Sepsis patients and Control subjects were included. An in vitro cellular model was established with LPS-stimulated THP- 1 cells. RT-qPCR assessed CYP1B1-AS1 and miR- 18a- 5p expression. ROC analysis evaluated diagnostic and predictive value. Kaplan-Meier curves and Cox regression analyzed the prognostic value of CYP1B1-AS1. Flow cytometry and ELISA assessed cell apoptosis and inflammatory factors levels. Dual luciferase reporter, RIP, and RNA pull down to validate target binding relationship. RESULTS: The GSE217700 database shows that CYP1B1-AS1 was upregulated in sepsis. Serum levels of CYP1B1-AS1 were higher in sepsis patients than controls. CYP1B1-AS1 was positively correlated with SOFA and APACHE II scores and distinguished sepsis patients from controls. The 28-day mortality rate for sepsis patients was 29.31%. High CYP1B1-AS1 expression in sepsis patients predicts a worse prognosis and is a potential risk factor. CYP1B1-AS1 targets miR- 18a- 5p. Silencing CYP1B1-AS1 reduced LPS-inducted apoptosis and inflammatory factor promotion, which the miR- 18a- 5p inhibitor reversed. CONCLUSION: CYP1B1-AS1 serves as a biomarker for sepsis diagnosis and poor prognosis, potentially promoting inflammation and apoptosis by targeting miR- 18a- 5p.