Background and objectives. Sepsis is a life-threatening organ dysfunction caused by the imbalance of the body’s response to infection. Delay in sepsis diagnosis has become a primary cause of patient death. This study aims to identify potential biomarkers of sepsis based on bioinformatics data analysis, so as to provide new gene biomarkers for the diagnosis and treatment of sepsis. Methods. Gene expression profiles of GSE13904, GSE26378, GSE26440, GSE65682, and GSE69528 were obtained from the National Center for Biotechnology Information (NCBI). The differentially expressed genes (DEGs) were searched using limma software package. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs and screen hub genes. Results. A total of 108 DEGs were identified in the study, of which 67 were upregulated and 41 were downregulated. 15 superlative diagnostic biomarkers (CCL5, CCR7, CD2, CD27, CD274, CD3D, GNLY, GZMA, GZMH, GZMK, IL2RB, IL7R, ITK, KLRB1, and PRF1) for sepsis were identified by bioinformatics analysis. Conclusion. 15 hub genes (CCL5, CCR7, CD2, CD27, CD274, CD3D, GNLY, GZMA, GZMH, GZMK, IL2RB, IL7R, ITK, KLRB1, and PRF1) have been elucidated in this study, and these biomarkers may be helpful in the diagnosis and therapy of patients with sepsis.