[Objective] Bioinformatics methods were used to analyze the whole blood transcriptome data of patients diagnosed with bacterial sepsis from public databases, and we explored the hub genes related to bacterial sepsis and their clinical significance.[Methods] The datasets GSE80496 and GSE72829 were obtained from Gene Expression Omnibus (GEO). GEO2R, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were applied to screen out the differentially expressed genes (DEGs) among the patients with bacterial sepsis, when compared to the healthy. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis were also performed on the key genes by R software, hubs genes were obtained by using String 11.0 and Cytoscape subsequently. In addition, the dataset GSE72809 was involved to verify the expression profiles of hub genes in whole blood samples among infants. And the relationships between gene expression and samples' baseline data (such as:gender, gestational age, birth weight, and antibiotic exposure) were also discussed in the study.[Results] 932 DEGs were screened out in GSE80496 dataset, while 319 DEGs were screened out in GSE72829 dataset. We identified 10 hub genes (MMP9, ITGAM, CSTD, GAPDH, PGLYRP1, FOLR3, OSCAR, TLR5, IL1RN and TIMP1). GSEA analysis shows key pathways (amino acid carbohydrate ribose metabolism, PPAR signaling pathway, glycan biosynthesis, autophagy regulatory pathway, complement/coagulation factor cascade reaction, nicotine and nicotinamide metabolism, unsaturated fatty acids biosynthesis and Alzheimer's disease pathway) and biological processes (steroid hormone secretion, adenylate cyclase activation, extracellular matrix degradation and metal ion transport) associated with bacterial sepsis.[Conclusion]] Through the analysis of GEO2R, GSEA combined with WGCNA, our study screened out 2 pivotal modules, 10 hub genes, several signaling pathways and biological processes closely related to bacterial sepsis, which may lay a theoretical basis for further research on the pathogenesis of bacterial sepsis.