BackgroundSepsis originates from the host's dysregulated response to pathogens, and its pathophysiological mechanisms are extremely complex. Recent research has found that post-translational modifications (PTMs) can regulate gene transcription without altering the genetic sequence, thereby playing a key role in the occurrence and development of sepsis.ObjectiveThis review aims to systematically categorize the main types of PTMs and elucidate their roles in the pathogenesis of sepsis, thereby providing new perspectives for a deeper understanding of the complex pathophysiological processes of this disease.MethodsWe searched databases including PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI), covering the period from their establishment to July 2025. The search strategy combined keywords related to "sepsis" (such as "sepsis", "septic shock") and "post-translational modifications" (such as "PTM", "lactylation", "acetylation", "methylation", "phosphorylation", "ubiquitination", "glycosylation"). After removing duplicates and low-quality literature, the remaining articles were analyzed and summarized to ultimately complete the writing of this review.ResultsPTMs exert profound influences on the inflammatory process, immune cell function, cell death modes, and energy metabolism in sepsis by regulating key effector molecules and signaling pathways. Research indicates that PTMs play a dual role in this process, which can either exert protective effects or lead to destructive outcomes.ConclusionPTMs represent a core regulatory mechanism in the pathophysiology of sepsis. A comprehensive understanding of the functions and interactions of various PTMs is of great significance for profoundly elucidating the complexity of sepsis and developing novel therapeutic strategies.