The utilization of different macronutrients is relevant for the risk of obesity, diabetes, or the appearing of vascular complications. The Respiratory Quotient (RQ) is a parameter measuring the fuel utilizations; in fact, it can indicate the fat stores utilization or lipogenesis activation. Aim of this study was to investigate the link between the RQ and the subclinical carotid atherosclerosis presence in overweight/obese subjects. 132 subjects with body mass index at least 25, at conventional diet, underwent an Indirect Calorimetry for the measurement of the Resting Metabolic Rate as well as the RQ and an evaluation of carotid arteries with ultrasound. Biochemical analyses were also performed. The mean age was 48 ± 12 years. There was a positive relation between carotid intima-media thickness and RQ (p = 0.010), with the high value in the subgroup with high RQ (p = 0.045 vs. group with low RQ). The RQ, an index of fuel utilization, is positively associated to subclinical carotid atherosclerosis in overweight/obese individuals.