Pyroptosis is a new form of programmed cell death recognized as crucial in developing sepsis. However, there is limited research on the mechanism of pyroptosis-related genes in sepsis-related from the Gene Expression Omnibus (GEO) database and standardized. The expression levels of pyroptosis-related genes were extracted, and differential expression analysis was conducted. A prediction model was constructed using random forest (RF), support vector machine (SVM), weighted gene co-expression new analysis (WGCNA), and nomogram techniques to assess the risk of sepsis. The relationship between pyroptosis-related subgroups and the immune microenvironment and inflammatory factors was studied using consistent clustering algorithms, principal component analysis (PCA), single-sample genomic enrichment analysis (ssGSEA), and immune infiltration. A risk prediction model based on 3 PRGs has been constructed and can effectively predict the risk of sepsis. Patients with sepsis can be divided into two completely different subtypes of pyroptosis-related clusters. Cluster B is highly correlated with the lower proportion of Th17 celld and has lower levels of expression of inflammatory factors. This study utilizes mechanical learning methods to further investigate the pathogenesis of sepsis, explore potential biomarkers, provide effective molecular targets for its diagnosis and treatment of sepsis.Copyright: © 2023 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.