To characterize fuel utilization of patients with congestive heart failure (CHF), we measured serum free fatty acid (FFA), counterregulatory hormone concentrations, whole body substrate oxidation rates (indirect calorimetry), and the turnover and oxidation rates of FFA ([1-¹⁴C]-palmitate infusion) in 7 patients with CHF and in 7 cardiac patients without CHF after an overnight fast. Plasma glucose and serum insulin concentrations were comparable, whereas serum FFA, blood ketone body, and fasting blood lactate (p <0.05 for all) concentrations were significantly increased in patients with CHF compared to those without CHF. Fasting plasma norepinephrine (p <0.05), serum cortisol (p <0.01), and growth hormone (p <0.01) concentrations were also higher in patients with CHF than in those without CHF. Rates of energy expenditure at rest (62 ± 2 vs 56 ± 1 J · kg⁻¹ · min⁻¹, p <0.05), FFA turnover (6.5 ± 0.5 vs 5.0 ± 0.4 μmol · kg⁻¹ · min⁻¹, p <0.05), and oxidation (2.0 ± 0.2 vs 1.5 ± 0.1 μmol · kg⁻¹ · min⁻¹, p <0.05) were significantly higher in patients with CHF than in control subjects. In univariate analysis, the left ventricular ejection fraction was inversely correlated and the plasma norepinephrine concentration positively correlated with both energy expenditure at rest, FFA turnover, and the FFA oxidation rate. In multivariate analysis, the plasma norepinephrine concentration was the most significant predictor of increased FFA oxidation rate. We conclude that release of FFAs to the circulation and their subsequent oxidation are increased in patients with severe CHF after an overnight fast. These changes might reflect stress hormone-induced lipolysis and accompanying stimulation of serum FFA oxidation via mass action.