['The present study aimed to evaluate the changes in the serum N-glycome profiles in chronic hepatitis B (CHB) patients and to assess the role of N-glycome-derived markers in the noninvasive diagnosis of liver fibrosis.', 'After liver biopsy for pathological grading and staging, 128 CHB patients underwent serum N-glycomic analysis using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) and sensitive markers were screened.', 'Peaks 1, 2, 8 and 10 in the N-glycome profiles could, to some extents, distinguish liver fibrosis at different stages. In addition, the N-glycome-derived marker log(peak2/peak8) possessed the highest diagnostic accuracy. The areas under the receiver operating characteristic (AUROCs) curves of the log(peak2/peak8) were 0.675, 0.736 and 0.754 in the diagnosis of significant fibrosis, advanced fibrosis and early cirrhosis, respectively. In combination with some marker panels (SLFG, S index, Fibrometer, Hui, Forns, APRI and Hepascore), it showed the best diagnostic potency in distinguishing significant fibrosis (SLFG + log[peak2/peak8], AUROC = 0.813) from advanced fibrosis (SLFG + log[peak2/peak8], AUROC = 0.899) and a better diagnostic potency in the identification of early cirrhosis (S index + log[peak2/peak8], AUROC = 0.903, lower than Hui model [AUROC = 0.927]) in the validation cohort.'] Does serum N-glycomic markers in combination with panels improve the diagnosis of chronic hepatitis B?