Background: Resting Energy Expenditure (REE) represents the largest component of total daily energy expenditure. While fat-free mass (FFM) is its primary predictor, substantial interindividual variability remains unexplained. The sympathetic nervous system has been implicated in the regulation of energy expenditure, but its contribution to REE under fasting conditions in humans is not yet determined. Methods: We investigated the relative contributions of body composition, circulating catecholamines, and cardiac autonomic modulation to REE in 38 healthy young participants following an overnight fast. REE was assessed by indirect calorimetry and FFM by bioelectrical impedance analysis. Cardiac autonomic activity was quantified through heart rate variability (HRV) analysis (time- and frequency-domain). Plasma epinephrine and norepinephrine were determined in a subsample (n = 19). Results: In a multivariable model including FFM, sex, and age, FFM was the dominant determinant of REE (R-2 = 0.90, p < 0.001). Sex contributed independently, whereas age showed no significant association. Circulating epinephrine was positively associated with REE (p = 0.024), while norepinephrine was not. None of the HRV-derived parameters was significantly associated with REE. Conclusion: Under basal fasting conditions, REE is primarily associated with FFM, with an additional association with circulating epinephrine. Given the absence of associations with norepinephrine and HRV-derived parameters, the findings suggest a potential role of circulating catecholamines in interindividual variability in REE. However, direct conclusions regarding the physiological mechanisms involved cannot be drawn from the present observational study. HRV-derived cardiac autonomic markers were not associated with REE under standardized fasting conditions.