Background <p>Sepsis remains a leading cause of global morbidity and mortality, yet early diagnosis is hindered by the limited specificity and sensitivity of current biomarkers.</p> Aim <p>The aim of this study was to identify lncRNAs that play a key role in sepsis and provide potential biomarkers for the diagnosis and treatment of sepsis.</p> Methods <p>Transcriptomic data from sepsis patients were retrieved from the Chinese National Genebank (CNGBdb). Differential expression analysis identified 2,348 LncRNAs and 5,125 mRNAs (|FC|≥2, FDR &lt; 0.05). Weighted gene co-expression network analysis (WGCNA) and meta-analysis were applied to screen core genes. Gene set enrichment analysis (GSEA) explored functional pathways, while single-cell sequencing and qPCR validated cellular localization and expression patterns.</p> Results <p>WGCNA identified three key genes: LINC02363 (LncRNA), DYNLT1, and FCGR1B. Survival and meta-analyses revealed strong correlations between these genes and sepsis outcomes. GSEA highlighted LINC02363’s involvement in “herpes simplex virus type 1 infection,” “tuberculosis,” and ribosome pathways. Single-cell sequencing showed FCGR1B’s broad distribution across immune cells, while DYNLT1 localized predominantly in macrophages. qPCR confirmed significant upregulation of LINC02363 (<i>p</i> &lt; 0.01), FCGR1B (<i>p</i> &lt; 0.05), and DYNLT1 (<i>p</i> &lt; 0.05) in sepsis patients compared to controls.</p> Conclusion <p>LINC02363 may serve as a new biomarker for the diagnosis and treatment of sepsis.</p>