This study was performed to evaluate the combined effect of a meal replacement and an alleged weight loss supplement (WLS) on body composition, fitness parameters, and clinical health in moderately overweight college-aged men and women. Body mass, bench press 1 repetition maximum (1RM), leg press 1RM, body composition, V(O2)max, fasting glucose (GLU), and lipid panels were evaluated before (T1) and after (T2) 8 weeks of combined resistance training (RT) and cardiovascular training (CVT). After T1, subjects were randomly assigned in a double-blind fashion to either the WLS (6 men, 7 women; 21 ± 5 years, 168 ± 8 cm, 75.4 ± 12.7 kg, 31.6 ± 7.7%BFAT) or placebo (PLA: 6 men, 6 women; 22 ± 4 years, 174 ± 9 cm, 84.1 ± 8.8 kg, 30.2 ± 5.6%BFAT) group. Both groups performed 3 d · wk(-1) of combined progressive RT (2 × 12 reps of 8 exercises at 75-80% 1RM) and CVT (30 minutes on a cycle ergometer at 70-85% heart rate reserve). Subjects consumed 4 capsules per day and a once-daily meal replacement throughout the protocol. Percent body fat, bench press 1RM, and leg press 1RM significantly improved (p < 0.05) in both groups. Blood GLU (G × T; p = 0.048) improved in WLS and systolic blood pressure (SBP) approached significance (G × T; p = 0.06) in the WLS group. Follow-up analysis of SBP revealed a significant within-group decrease in the WLS group, whereas no within-group changes were found for either group for GLU. Practically speaking, daily supplementation with a meal replacement and a thrice weekly exercise program can increase fitness levels and improve body composition, whereas adding a thermogenic substance provides no additional benefit over fitness or body composition changes but may favorably alter serum markers of clinical health.