An enduring enigma is why the ratio of resting energy expenditure (REE) to metabolically active tissue mass, expressed as the REE/fat-free mass (FFM) ratio, is greater in magnitude in subjects with a small FFM than it is in subjects with a large FFM. This study tested the hypothesis that a higher REE/FFM ratio in subjects with a small body mass and FFM can be explained by a larger proportion of FFM as high-metabolic-rate tissues compared with that observed in heavier subjects. REE was measured by indirect calorimetry, FFM by dual-energy X-ray absorptiometry (DEXA), and tissue/organ contributions to FFM by whole body magnetic resonance imaging (MRI) in healthy adults. Four tissue heat-producing contributions to FFM were evaluated, low-metabolic-rate fat-free adipose tissue (18.8 kJ/kg), skeletal muscle (54.4 kJ/kg), and bone (9.6 kJ/kg); and high-metabolic-rate residual mass (225.9 kJ/kg). Initial evaluations in 130 men and 159 women provided strong support for two key, developed models, one linking DEXA FFM with MRI FFM estimates and the other linking REE predicted from the four MRI-derived components with measured REE. There was an inverse association observed between measured REE/FFM and FFM (r(2) = 0.17, P < 0.001). Allometric models revealed a similar pattern of tissue change relative to body mass across males and females with greater proportional increases in fat-free adipose tissue and skeletal muscle than in FFM and a smaller proportional increase in residual mass than in FFM. When examined as a function of FFM, positive slopes were observed for skeletal muscle/FFM and pooled low-metabolic-rate components, and a negative slope for residual mass. Our linked REE-body composition models and associations strongly support the hypothesis that FFM varies systematically in the proportion of thermogenic components as a function of body mass and FFM. These observations have important implications for the interpretation of between-individual differences in REE expressed relative to metabolically active tissue mass.