Objective: Exercise training may cause changes in thyroid function. This thyroid response may be due to exercise-induced modulation of energy metabolism but also of the adipocytes endocrine function. In particular, the role of leptin and of circulating soluble leptin receptor (sOB-R) was unexplored. The aim of this study was to assess the relationships between thyroid function, whole body energy metabolism, and adipokines -mainly leptin and its receptor, sOB-R. Methods: We measured serum TSH, free tri-iodothyronine (FT 3 ), free thyroxine, leptin, and sOB-R and assessed energy homeostasis by means of indirect calorimetry, in 27 highly trained athletes and 27 sedentary, healthy men. Results: TSH-FT 3 ratio was lower in athletes (P!0.03), either in sustained power or anaerobic powersprint athletes (nZ13) or marathon runners (nZ14). Whole body respiratory quotient was lower in athletes. Fasting serum sOB-R was higher and leptin lower in athletes than controls. Also serum adiponectin, resistin, and retinol binding protein-4 concentrations were different in athletes than in controls. The ratio between leptin and sOB-R, the free leptin index (FLI), was lower in athletes than in controls (0.025G0.014 vs 0.085G0.049; P!0.001). In multivariate analysis, FLI retained independent association with TSH-FT 3 ratio. Conclusion: Male, elite athletes had lower TSH-FT 3 ratio and FLI than controls while FLI was independently associated with TSH-FT 3 ratio supporting the hypothesis that the level of biologically active leptin is involved in the adaptive response of thyroid function in professional athletes.