Introduction: Ketone bodies have energetic advantages over other fuel substrates, and may alter oxidative fuel selection in working muscle by providing an alternative carbon source for respiration[1]. However the relationship between exercise intensity and the clearance (metabolic disposal) of ketone bodies from the bloodstream is unknown. Methods: After an overnight fast, 8 highly trained male endurance athletes (age 28.6 y, VO2 max 5.2 L/min) drank 0.573g/kg BW of ketone ester (KE), in a randomised crossover design. After 10 min, athletes performed 45 min of bicycle exercise at fixed intensities of 40% Wmax (Low), or 75% Wmax (High) on separate study days. Identical studies were also performed at rest. Blood samples were obtained via an intravenous catheter at regular intervals during exercise, and assayed for β-hydroxybutyrate (BHB), lactate, glucose and fats (FFA). Indirect calorimetry (Cortex, Metalyser) was performed at identical times to quantify respiratory quotient and VO2. Urinary excretion of BHB was determined from urine collections before and after exercise. A 3-way repeated measures ANOVA with post-Hoc Tukey corrections was used to determine statistical significance (considered as p<0.05). Results: Blood BHB rose from 0.1 to 2.7 ± 0.1 mM (p<0.01) 10 min following KE ingestion. BHB concentration increased at rest reaching ~6mM after 45 min. In contrast, circulating BHB concentrations fell with the onset of exercise, and were significantly reduced on High (2.4 ± 0.1 mM) vs. Low (3.3 ± 0.2 mM) intensity (p<0.05). BHB AUC was reduced in both high (50%) and Low (30%) vs. rest (p<0.05) after 45 min of exercise. An exponential decrease in BHB AUC was observed with increasing VO2 (r2 = 0.7, p<0.01). Only a small fraction of circulating BHB (0.1 ± 0.04 g) was eliminated in the urine. As expected, mean exercise lactate concentrations were greatest on High (3.6 ± 0.5 mM) vs. Low (1.2 ± 0.1 mM, p<0.05) and rest (1± 0.1mM, p<0.05). No differences in blood glucose and FFA were observed between study conditions. RQ and VO2 increased with increasing exercise intensity as would be expected (p<0.05 rest vs. low, High, and High vs. Low). Conclusion: Conventional calorimetric equations[2] to calculate substrate oxidation during exercise do not account for ketone bodies as an energy source. These data demonstrate an exponential increase in ketone blood ketone body clearance with increasing oxygen consumption, suggesting the hierarchy of muscular fuel selection was altered during incremental exercise in the presence of ketosis. Urinary elimination of ketone bodies in exercise was negligible and cannot explain the increase in metabolic disposal.