Sepsis is a severe systemic inflammatory response that poses a significant challenge in clinical diagnosis and treatment, with early identification being crucial for improving patient outcomes. This study aimed to investigate the N-glycosylation characteristics of immunoglobulin G (IgG) in the plasma of patients with sepsis via quantitative N-glycoproteomics. Using our developed GlycoQuant strategy based on EThcD-sceHCD-MS/MS, we quantified the intact N-glycopeptides (IGPs) of IgG subclasses from 40 healthy controls (HCs) and 40 patients with sepsis (S).