Sepsis is closely linked to immunity. Our research aimed to identify key genes associated with sepsis immunity utilizing single-cell RNA sequencing (scRNA-seq) data. This study obtained the GSE167363 and GSE54514 datasets from the Gene Expression Omnibus (GEO). The GSE167363 dataset was subjected to cluster analysis, cell proportion analysis, cell interaction analysis, and gene set enrichment analysis (GSEA). The differentially expressed genes (DEGs) of CD8+ T cells were intersected with the DEGs in the GSE54514 dataset, and key genes related to immunity in sepsis patients were identified through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, we validated the gene expression levels in a mouse model of sepsis caused by cecum ligation and puncture (CLP). Findings indicated that intercellular communication of Cytotoxic CD8+ T cells was reduced in the sepsis survivors compared to non-survivors. The expression of 3 down-regulated key DEGs (ITGB2, SELL and ICAM3) was negatively correlated with the abundance of CD8+ T cells. Moreover, Cytotoxic CD8+ T cells with low expression of ITGB2, SELL and ICAM3 were more adverse to the survival of sepsis as compared to those with high expression of the above genes. These genes may predict increased survival in sepsis by regulating intercellular communication in cytotoxic CD8+ T cells, suggesting that they are potential therapeutic targets for improving sepsis prognosis.