The purpose of this paper was to determine the effect of replacing breakfast with a high-fat drink on fat mass (FM), lean mass (LM), percent body fat (%BF), visceral fat (VAT), resting metabolic rate (RMR), fuel utilization (RER), blood lipids and satiety in overweight and obese adults. Healthy adults (n = 42; 21 Females; body mass index (BMI): 32.8 ± 4.6 kg·m-2) were randomized to control (CON; n = 21) or meal replacement (MRP; n = 22) groups. Body composition was measured using a four-compartment model; RMR and RER were assessed from indirect calorimetry. The MRP (70% fat) was consumed once daily for eight weeks. For males, there was no change (p > 0.05) in FM (mean difference (MD) = 0.41 ± 1.19 kg], %BF MD = 0.50 ± 1.09%, LM MD = -0.64 ± 1.79 kg, or VAT MD = -0.31 ± 1.36 cm for MRP versus CON. Similarly, no differences for females for FM MD = -0.73 ± 1.37 kg, %BF MD = -0.57 ± 1.26%, LM MD = 0.31 ± 1.37 kg, or VAT MD: -0.83 ± 1.2 cm. HDL was significantly reduced in the MRP group for females (adjusted mean change: -6.41 ± 4.44 units, p = 0.018). There was no effect on RMR or RER. Satiety increased in the afternoon for MRP (p = 0.021). Despite high fat, no negative impact on lipids resulted; increased satiety may be beneficial for controlling afternoon cravings, but does not affect body composition.