Abstract: Objective　To investigate the changes of serum Copeptin and matrix metalloproteinase-9 (MMP-9) in children with chronic heart failure (CHF) and its clinical significance. Methods　A total of 186 children with CHF were selected for CHF group, including 78 cases of cardiac function grade Ⅱ, 65 cases of grade Ⅲ, and 43 cases of grade Ⅳ. There were 57 cases of dilated cardiomyopathy, 68 cases of congenital heart disease and 61 cases of other diseases. Another 85 healthy children from health checkup were chosen as controls. The levels of serum Copeptin and MMP-9 were determined by enzyme linked immunosorbent assay (ELISA), and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by bidirectional lateral flow immunoassay. The left ventricular end diastolic dimension (LVEDD), left ventricular end systolic dimension (LVESD), left ventricular ejection fraction (LVEF), and left ventricular short fraction shortening (LVFS) were measured by echocardiography. ROC curve was used to analyze the diagnostic value of serum Copeptin and MMP-9 in CHF. The correlation of serum Copeptin and MMP-9 with the cardiac function indices were examined by Pearson correlation analysis. Results　The levels of serum copeptin, MMP-9, and NT-proBNP in different cardiac function groups (Ⅱ, Ⅲ, Ⅳ) increased gradually with the aggravation of the cardiac function damage and were higher than those in control group, and the differences were statistically significant (P<0.05). Compared with the control group and cardiac function grade Ⅱ group, the levels of LVESD and LVEDD were increased and the levels of LVEF and LVFS were decreased in the grade Ⅲ and Ⅳ groups. Compared with the grade Ⅲ group, the levels of LVESD and LVEDD were increased and the levels of LVEF and LVFS were decreased in the grade Ⅳ groups. There were significant differences (P<0.05). The ROC curve showed that the area under the curve (AUC) and 95% CI of serum Copeptin, MMP-9, NT-proBNP and combinations of these three biomarkers in the diagnosis of CHF were 0.845 (0.781~0.914), 0.806 (0.736~0.883), 0.894 (0.828~0.962) and 0.925 (0.846~0.983) respectively, and the optimal thresholds were 12.5 pmol/L, 175.3 μg/L and 2037.0ng/L. The level of serum Copeptin was positively correlated with MMP-9 (r=0.807, P<0.001). Conclusion　Serum Copeptin and MMP-9 may be involved in the ventricular remodeling in CHF children and they are expected to be a good indicator for the diagnosis of CHF and cardiac function.