The aim of this study was to characterize the metabolic profile of healthy, normal-weight adults presenting with low satiety responsiveness. Individuals were categorized with low or high satiety responsiveness (LSR and HSR, respectively) based on the satiety quotient (SQ), a marker of satiety responsiveness, which was calculated following two isocaloric breakfast test meals offered while participants were inside the whole-room indirect calorimeter (WRIC): 1) North American: 55% carbohydrate, 15% protein, and 30% fat; 2) High-protein: 31% carbohydrate, 43% protein, and 26% fat. Following the North American breakfast, participants continued receiving a diet resembling the North American dietary pattern while inside the WRIC for 32 consecutive hours where the following outcome measures were assessed: energy metabolism components, metabolic blood markers, and appetite sensations. Forty-three participants were included; 13 were classified as LSR (n=3 females; n=10 males), n=16 as HSR (n=10 females; n=6 males), and n=14 were uncategorized. Compared with HSR, individuals with LSR had higher body weight (5.4 ± 2.5 kg; P=0.042) and waist circumference (LSR: 77.5 (7.6) cm; HSR: 70.7 (5.2) cm; P=0.012). Participants with LSR presented with higher total energy expenditure (184 ± 85 kcal/day; P=0.040) and carbohydrate oxidation rate (34 ± 13 g/day; P=0.015). Moreover, individuals in the LSR category presented with weakened satiety response to the meals when compared to those with HSR. Our primary findings were that, compared to individuals with HSR, those in the LSR category exhibited differences in their metabolic profile. The long-term impact on body weight and overall health should be assessed in further studies.