Background: Understanding resting energy expenditure (REE) is important for determining energy requirements; REE might be altered in individuals with cancer. The objective of this study was to characterize determinants of REE in patients with stages II-IV colorectal cancer (CRC).Methods: REE was measured via indirect calorimetry in patients with newly diagnosed CRC. Computerized tomography images from medical records ascertained skeletal muscle and total adipose tissue cross-sectional areas, which were then transformed to lean soft tissue (LST) and fat mass (FM) values (in kg). Linear regression assessed determinants of REE.Results: 86 patients were included (n = 55, 64.0% male; 60 ± 12 years old; median body mass index: 27.6, interquartile range: 24.3-31.2 kg/m2), with most (n = 40) having stage III disease. Age, sex, and weight were significant predictors of REE [R2 = 0.829, standard error of the estimate (SEE): 128 kcal/day, P < 0.001]. Replacing weight with LST and FM yielded a similar model, with age, sex, LST, and FM predictive of REE (R2 = 0.820, SEE: 129 kcal/day, p < 0.001).Conclusion: Age, sex, weight, LST, and FM were the main contributors to REE. Further investigation of REE changes over time and its relationship to total energy expenditure, dietary intake, and clinical outcomes should be explored.