The aim of this review is to delve into the multilevel regulatory mechanisms of ubiquitination and deubiquitination in sepsis, focusing on the process by which PAMP and DAMP trigger inflammatory responses through activation of PRRs, and how they regulate the activity and function of key inflammatory proteins (e.g., RIPK1 and NF-κB) via the ubiquitination pathway. This evidence concerns the gene NFKB1 and Sepsis.