Background: Nighttime eating is often associated with metabolic syndrome and poor body composition and these conditions may be influenced by the natural decline in metabolism that occurs during sleep. However, only limited research has been conducted to determine the role of individual macronutrients at night. Previous research indicates that protein consumption increases metabolic rate more than carbohydrates or fat, and therefore may attenuate this decline when consumed at night before bed. In addition, digestion and absorption kinetics of a fast protein such as whey protein (WP) and a slow protein such as casein protein (CP) may independently influence appetite and body composition. Therefore, nighttime eating may be a window of opportunity to influence changes in body composition, strength, cardiovascular health, metabolism and appetite (hunger, desire to eat, and satiety). Purpose: To compare the effects of isocaloric maltodextrin placebo (PLA), WP and CP supplements when consumed immediately prior to nocturnal sleep when combined with four weeks of exercise training on body composition, strength, fasting glucose and lipid profiles, metabolism and appetite. Methods: Fifty-nine sedentary, overweight and obese participants were recruited and had baseline measurements of body composition (dual energy X-ray absorptiometry (DXA)), resting metabolism (ParvoMedics TrueOne 2400 metabolic cart), strength (1RM Chest- and Leg-press), blood glucose and lipid profiles (Cholestech LDX Analyzer) and appetite questionnaires (visual analogue scale) taken after an overnight fast (0600-0900 h). Forty-eight participants completed the four-week study protocol. The participants were randomly stratified by % body fat, BMI, and gender to one of three groups: PLA (n= 14, men: 4, BMI= 34.4 ± 1.5 kg/m2, age= 28.1 ± 1.8 years), WP (n= 17, men: 3, BMI= 34.3 ± 1.3 kg/m2, age= 30.1 ± 1.6 years), CP (n=17, men: 3, BMI= 35.4 ± 1.3 kg/m2, age= 30.1 ± 1.6 years) in a double blind design. Participants were then instructed to consume their supplement at least two hours after dinner and no more than 30 minutes before bed each night for four weeks. All participants attended supervised exercise sessions (3x/week; 2 days of resistance exercise and 1 day of high-intensity cardiovascular exercise). Post-testing occurred 36-60 hours after the last supplementation and 96-144 hours after the final training session. A one-way ANOVA was performed to examine possible group differences at baseline and differences in change among groups. A two-way ANOVA with repeated measures was used to evaluate changes in dependent variables over time ([pre x post] x [PLA x WP x CP]). A Tukey test was used for post hoc comparisons. Values are reported as means ± SEM. Significance was accepted at P<0.05. Results: Eleven participants who completed baseline measurements failed to complete the four-week protocol and maintain satisfactory compliance with exercise and supplement intake (< 80% compliance). With the exception of fasting glucose, no significant group differences existed at baseline. There were no group x time interactions for resting metabolic rate (RMR), hunger, satiety, desire to eat, fat mass, lean body mass, BF%, or weight, although RMR displayed a trend (P=0.0559) towards significance with the PLA group decreasing by 74.3 ± 94.5 kcal/day and WP and CP increasing by 235.7 ± 84.5 kcal/day and 51.7 ± 79.4 kcal/day, respectively. Additionally, there was a group x time effect for VO2 with WP increasing by 0.3 ± 0.1 ml/kg/min compared with a decrease of 0.1 ± 0.1 ml/kg/min and an increase of 0.1 ± 0.1 ml/kg/min for PLA and CP, respectively. Significant time effects were measured for satiety (pre: 31.5 ± 2.3 mm, post: 40.6 ± 2.3 mm, P< 0.008) and lean body mass (LBM) (pre: 51.8 ± 0.1 kg, post: 52.3 ± 0.1 kg, P< 0.0001). Conclusion: In conclusion, our data indicate exercise three times per week for four weeks combined with nighttime eating can be a successful method for improving LBM, BF%, strength, and satiety in previously sedentary, overweight and obese individuals. Additionally, four weeks of nighttime WP supplementation may elevate VO2 36-60 hours after the last supplementation.