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Objective·Previous studies showed that hepatitis B virus (HBV) infection caused outstanding changes in host lipoproteins. However, there are no reports on such component changes of lipoprotein subfractions. This study aimed to quantify the HBV-caused changes in the serum lipoprotein subfractions and their components.Methods·Hepatitis B surface antigen-positive [HBsAg (+)] patients at Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March to June 2017 were included (n=40), and 40 HBsAg-negative [HBsAg (-)] population were matched as controls. Serum lipoprotein subfractions and their components were quantified by using 1H-NMR. Orthogonal partial least-squares discriminant analysis (OPLS-DA), variance analysis between the two groups, logistic regression analysis and Spearman correlation analysis were conducted to reveal the lipoprotein changes in chronic HBV patients against controls.Results·HBsAg (+) population had significantly lower levels in most lipoprotein subfractions than HBsAg (-) population. After adjustments for age, gender, hypertension, diabetes mellitus and coronary heart disease, the levels of total VLDL, VLDL1-VLDL3, IDL, HDL4, non-HDL and their components were protective factors for HBV infection (OR < 1, P < 0.01). In contrast, VLDL5-(TAG/LP) was a risk factor for HBV infection (OR > 1, P < 0.01). In addition, the severity of inflammation in the HBsAg (+) population was negatively correlated with the levels of lipids in HDL4 with correlation coefficient ranging from -0.71 to -0.51 (P≤ 0.002). Six lipoprotein subfractions were obtained through feature screening, and the AUC of HBV infection diagnosis model was 0.861.Conclusion·HBV infection causes significant changes in liver-excretion of lipoproteins and their circulation metabolism; the lipoprotein phenotypes can differentiate HBV-infected patients from controls.