Objective: Proteins are the major effectors of biological structure and function. Oxidation-induced changes to protein structure can critically impair protein function, with important pathologic consequences. This study was undertaken to examine whether oxidation-induced changes to protein structure occur during pediatric cardiopulmonary bypass and to examine the association with postoperative outcome. Methods: Elevation of the 3,4-dihydroxy-phenylalanine content of a protein relative to its native tyrosine content indicates structural damage due to oxidation. Protein 3,4-dihydroxyphenylalanine/ native tyrosine ratios were measured before surgery and up to 6 hours after institution of cardiopulmonary bypass in 24 children undergoing repair of congenital heart disease, who were prospectively selected to form a cyanotic and comparable acyanotic control group. Results were correlated with perioperative variables and postoperative outcomes. Results: Elevation of protein 3,4-dihydroxyphenylalanine/tyrosine ratios above baseline(0.48 mmol/mol SD, 0.11 mmol/mol vs 0.36 mmol/mol SD, 0.13 mmol/mol ;P=.001) occurred within 30 minutes of initiating cardiopulmonary bypass in cyanotic but not in acyanotic children and correlated inversely with preoperative arterial oxygen saturation(R=-0.52; P=.03). Protein 3,4-dihydroxyphenylalanine/ tyrosine ratios were also increased above baseline at 120 minutes(0.44 mmol/mol SD, 0.12 mmol/mol ; P=.007) and 180 minutes(0.40 mmol/mol SD, 0.14 mmol/mol ; P=.01) after the institution of cardiopulmonary bypass in children who underwent prolonged procedures. Elevation of 3,4-dihydroxyphenylalanine/tyrosine during prolonged procedures was associated with postoperative arrhythmias and the need for increased inotropic support(P=.001). Conclusions: Oxidative injury to proteins occurs during pediatric cardiopulmonary bypass. Cyanotic children are most at risk, particularly those undergoing prolonged procedures, in whom elevation of the protein 3,4-dihydroxyphenylalanine/tyrosine ratio is associated with increased postoperative morbidity. Objective: Proteins are the major effectors of biological structure and function. Oxidation-induced changes to protein structure can critically impair protein function, with important pathologic consequences. This study was undertaken to examine whether oxid-induced changes to protein structure occur during pediatric cardiopulmonary bypass. and to examine the association with postoperative outcome. Methods: Elevation of the 3,4-dihydroxy-phenylalanine content of a protein relative to its native tyrosine content indicates that structural damage due to oxidation. Protein 3,4-dihydroxyphenylalanine / native tyrosine ratios were measured before surgery and up to 6 hours after institution of cardiopulmonary bypass in 24 children undergoing repair of congenital heart disease, who were prospectively selected to form a cyanotic and comparable acyanotic control group. Results were correlated with perioperative variables and postoperative outcomes. Results: Elevation of protein 3,4-dihydroxyphenyl alanine / tyrosine ratios above baseline (0.48 mmol / mol SD, 0.11 mmol / mol vs 0.36 mmol / mol SD, 0.13 mmol / mol; P = .001) occurred within 30 minutes of initiating cardiopulmonary bypass in cyanotic but not in acyanotic children and The correlation of protein 3,4-dihydroxyphenylalanine / tyrosine ratios were also above baseline for 120 minutes (0.44 mmol / mol SD, 0.12 mmol / mol; P = .03) .007) and 180 minutes (0.40 mmol / mol SD, 0.14 mmol / mol; P = .01) after the institution of cardiopulmonary bypass in children who underwent prolonged procedures. Elevation of 3,4-dihydroxyphenylalanine / tyrosine during prolonged procedures was associated with postoperative arrhythmias and the need for increased inotropic support (P = .001). Conclusions: Oxidative injury to proteins occurs during pediatric cardiopulmonary bypass. Cyanotic children are most at risk, particularly those undergoing prolonged procedures, in whom elevation of the protein 3, 4-dihydroxyphenylalanine / tyrosine ratio is associated with increased postoperative morbidity.