OBJECTIVE To compare weight loss, body composition, and metabolic changes in response to carbohydrate versus dietary energy restriction (DER) in obese mice. METHODS One hundred C57BL/6 mice were randomized into five groups of 20. The group of high-carbohydrate (HC) mice consumed an HC diet ad libitum and the group of high-fat (HF) mice consumed an HF diet ad libitum for 14 weeks. Additional groups consumed the HF diet for 7 weeks ad libitum and during weeks 8-14 were switched to either a low-carbohydrate diet (LC) consumed ad libitum, the HC diet pair-fed (PF) to the energy intake of the LC group, or an HC DER regimen providing 70% of the energy intake of the HF group. RESULTS At 14 weeks, the LC and HF groups weighed more and exhibited higher percent fat mass and lower bone mineral density than the HC, PF, and DER groups. Relative to the DER group, the LC group displayed comparable serum ketone bodies but higher serum glucose, triglycerides, cholesterol, leptin, insulin, and insulin-like growth factor-1. CONCLUSIONS In contrast to DER, the LC diet did not cause weight loss or reduce serum markers associated with obesity-related diseases other than diabetes in obese mice, suggesting that carbohydraterestriction without reduced energy intake does not induce weight loss.