Background: Data concerning the effects of afternoon snacking on ingestive behavior, mood, and cognition are limited. Objective: The purpose of this study was to compare 1088 kJ of high-protein (HP) or high-fat (HF) afternoon snacks vs. no snacking on appetite, food intake, mood, and cognition in adolescents. Methods: Thirty-one healthy adolescents (age: 17 +/- 1 y) consumed the following afternoon snacks (in randomized order) for 3 d: HP snack (26 g of protein/6 g of fat per 27 g of carbohydrates), HF snack (4 g of protein/12 g of fat per 32 g of carbohydrates), and no snack (NoS). On day 4 of each treatment, the participants completed an 8-h testing day containing pre- and postsnack appetite questionnaires, food cue stimulated functional MRI brain scans, mood, cognitive function, and eating initiation. Ad libitum dinner and evening snacks were provided and assessed. Results: HP, but not HF, delayed eating initiation vs. NoS (P < 0.05). Both snacks reduced appetite vs. NoS (P < 0.001) with HP eliciting greater reductions than HF (P < 0.05). Only HF led to reductions in corticolimbic activation in brain regions controlling food motivation/reward vs. NoS (P < 0.01). Although no treatment differences in daily energy intake were detected, HP led to greater protein consumption than NoS (P < 0.05) and greater protein and lower fat consumption than HF (both, P < 0.05). HP led to fewer HF/high-sugar evening snacks than NoS (P <0.01) and HF (P = 0.09). Although no treatment effects were detected for mood and cognition, HP tended to reduce confusion-bewilderment (P = 0.07) and increase cognitive flexibility (P = 0.09), whereas NoS reduced tension-anxiety (P < 0.05) and vigor-activity (P < 0.05). Conclusion: Afternoon snacking, particularly on HP soy foods, improves appetite, satiety, and diet quality in adolescents, while beneficially influencing aspects of mood and cognition.