Cardiac-related death has been reported following strenuous exercise, and biochemical markers predicting adverse outcomes would be useful. Despite the fact the myeloperoxidase (MPO) release may precede myocardial injury and identify at-risk patients earlier than traditional markers, information on the effects of marathon running on MPO levels is lacking. We measured MPO in conjunction with the creatine kinase MB fraction (CK-MB), myoglobin, troponin T (TnT), and N-terminal B-type natriuretic peptide (NT-proBNP) in 24 athletes before and after a marathon race. Of the 24 athletes, 22 (92%) had an increased MPO level, and the mean MPO level increased from 281.44 pmol/L to 785.21 pmol/L (P < .0001). Results for 14 (58%) of the athletes reached or exceeded the manufacturer's recommended clinical threshold. The increases in CK-MB, myoglobin, TnT, and NT-proBNP also reached statistical significance. Although the elevation in MPO most likely represents a systemic inflammatory response, the concurrent elevations in TnT and NT-proBNP suggest that myocardial injury cannot be excluded.