BACKGROUND Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD). METHODS We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers. RESULTS Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst). CONCLUSIONS NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.