This prospective, single-centre cohort study aimed to evaluate plasmin generation and fibrinolysis during and after cardiopulmonary bypass (CPB) surgery in a cohort of children up to 6 years of age. Blood samples were drawn at eight time points: after induction of anesthesia, before unfractionated heparin (UFH), after UFH, after initiation of bypass, before protamine, after protamine, after chest closure, and 6 h after chest closure. The study identified an increase in fibrinolysis during CPB and particularly up to 6 h afterward in children. This could be the mechanism for the significant bleeding events observed in this young population after CPB. This study establishes the foundation for future studies in this area, particularly those focusing on clinical outcomes after CPB surgery.