Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism. Using targeted metabolomic examinations, we investigated amino acid metabolism in a homogeneous adult Fontanpatient group with a dominant left ventricle, seeking biomarker patterns that might permit better understanding of fontan pathophysiology and early detection of subtle ventricular or circulatory dysfunction. We compared serum amino acid levels (42 analytes; AbsoluteIDQ p180 kit, Biocrates Life Sciences, Innsbruck, Austria) in 20 adult Fontan patients with a dominant left ventricle and those in age-and sex-matched biventricular controls. Serum concentrations of asymmetric dimethylarginine, methionine sulfoxide, glutamic acid, and trans-4-hydroxyproline and the methionine sulfoxide/ methionine ratio (Met-SO/Met) were significantly higher and serum concentrations of asparagine, histidine, taurine, and threonine were significantly lower in patients than in controls. Met-SO/ Met values exhibited a significant negative correlation with oxygen uptake during exercise. The alterations in amino acid metabolome that we found in fontan patients suggest links between fontan pathophysiology, altered cell energy metabolism, oxidative stress, and endothelial dysfunction like those found in biventricular patients with congestive heart failure. Studies of extended amino acid metabolism may allow better understanding of fontan pathophysiology that will permit early detection of subtle ventricular or circulatory dysfunction in Fontan patients. Ventricular dysfunction and circulatory failure with progressing end-organ impairment like renal or liver dysfunction are an important cause of morbidity and mortality in adults with complex congenital heart disease (CHD), especially in patients with single-ventricle types of CHD and Fontan circulation 1,2. Besides limited cardiac output, alterations that mark Fontan hemodynamics are passive flow to the lungs, chronically elevated venous pressures, and congestion. Unfortunately, the clinical use of traditional markers such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels for non-invasive diagnostics and monitoring in such patients is limited 3,4. Thus, for early detection of cardiac and circulatory derangement and for evaluation and tailoring of treatment options, regular functional assessment of these patients is crucial, with complete clinical examination, electrocardiogram, imaging studies, determination of values for traditional laboratory markers, or exercise capacity testing.