Existing reports on the association between oxidative stress and pulmonary hemodynamics in congenital heart disease (CHD) are limited, and the relationship remains inadequately understood. To address this, we evaluated the link between oxidative stress and hemodynamics in children with left-to-right shunt CHD. We analyzed the derivatives of reactive oxygen metabolites (d-ROMs) in a cohort of 60 children with left-to-right shunt CHD and compared them to 60 healthy, age- and sex-matched controls. In the CHD group, hemodynamics measured by cardiac catheterization were evaluated in relation to d-ROMs. We also assessed the diagnostic performance of the d-ROMs for a pulmonary-to-systemic blood flow ratio (Qp/Qs) of >1.5. We found that the blood d-ROM levels in the CHD group were significantly higher than those in the control group (p < 0.001). A significant positive correlation was observed between d-ROMs and Qp/Qs (p < 0.001), d-ROMs and the ratio of the right ventricular end-diastolic volume (p < 0.001), d-ROMs and the mean pulmonary arterial pressure (p < 0.001), and d-ROMs and the ratio of the left ventricular end-diastolic volume (p = 0.007). In the receiver operating characteristic curve analysis, the area under the curve for d-ROMs in predicting Qp/Qs > 1.5 was 0.806 (p < 0.001), which, although not statistically significant, was higher than that of the plasma N-terminal pro-brain natriuretic peptide (0.716). These findings indicate that d-ROM levels are closely associated with hemodynamics and the disease severity in patients with left-to-right shunt CHD and may serve as a valuable marker for determining the need for surgical intervention.