A buffer placed in brief contact in the skin was assayed by 1H NMR spectroscopy. We found that this passive extraction of the skin surface yields abundant metabolites. Metabolites of the skin surface originate from a variety of sources, including the sweat gland, which produces lactate from the glucose received from its capillary bed. Little is known about how metabolites resident on and within the skin surface respond to a metabolic or hemodynamic perturbation. As a possible application of epidermal metabolite profiling, we asked whether metabolites extracted from the skin surface are indicative of heart failure. The levels of lactate and other molecules were significantly lower in patients in heart failure than in individuals who reported healthy heart function, possibly due to reduced blood flow to the sweat gland resulting in a lack of tissue perfusion. Most amino acids were unchanged in levels, except for glycine and serine that increased as a percentage of all amino acids. These results have the potential in the long term to help decide the extent to which a patient has heart failure for which objective measures are lacking. Moreover, the results suggest that epidermal metabolite profiling may be useful for other assessments of human health.