<b>Background/Objectives</b>: In the present study, we hypothesized that cardiac surgery in pediatric patients with congenital heart disease (CHD) leads to profound endothelial glycocalyx degradation, measured as the increase in plasma syndecan-1 concentration, and that this endothelial damage is more pronounced in patients with cyanotic CHD. This evidence concerns the gene SDC1 and congenital heart disease.