OBJECTIVE: To examine the effects of a sugar-only (SO) beverage vs one containing a mixed-nutrient (MN) composition on energy expenditure and feelings of hunger and satiety. HYPOTHESIS: A beverage containing a mixed macronutrient composition will lead to greater thermic effect of food and feelings of fullness than an isocaloric beverage containing only sugar. RESEARCH METHODS AND PROCEDURES: Adults were randomly assigned to receive a 2510 kJ (600 kcal) SO liquid formula followed by an isovolumic, isoenergetic, MN liquid formula with an energy distribution of 17% protein, 67% carbohydrates as sucrose and corn syrup solids, and 16% fat, or vice versa, in a crossover design. The carbohydrate source in the two beverages was identical: 1: 1 ratio of sucrose and corn syrup solids (25 dextrose equivalents). The thermic response was calculated as the 7 h deviation from resting metabolic rate (RMR). Subjects provided hunger/satiety ratings and other related information by visual analog scales at regular intervals throughout the study period. RESULTS: In all, 20 subjects completed the protocol; one was removed from the thermic effect analysis due to discrepant RMRs. Following beverage ingestion, SO and MN liquid meals produced 7 h thermic effects of (X +/- s.e.m.) 274.1 +/- 27.6 kJ (65.5 +/- 6.6 kcal) and 372.0 +/- 33.9 kJ (88.9 +/- 8.1 kcal), respectively, resulting in a significant (P < 0.01) difference between meals (Delta = 97.9 +/- 35.1 kJ [23.4 +/- 8.4 kcal]). Analysis of satiety ratings using area under the curve analysis showed greater feelings of satiety (P < 0.05) with MN compared to SO consumption. Also, subjects felt that they could eat less (P < 0.05) after consumption of the MN vs SO beverage. DISCUSSION: In comparison to MN beverages, SO beverages are associated with a relatively high-energy retention without accompanying subjective hunger/fullness compensations, suggesting a basis for their role in long-term unintentional weight gain in healthy adults.