Metabolic adjustments occur with weight loss that may contribute to a high rate of weight regain. We have previously observed in obesity-prone, obese rats that weight reduction is accompanied by a suppression in resting metabolic rate beyond what would be predicted for the change in metabolic mass. In the present study, we examine if this adjustment in metabolic efficiency is affected by the length of time in weight maintenance and if it contributes to the propensity to regain after weight loss. Twenty-four-hour, nonresting, and resting energy expenditure (REE) were obtained by indirect calorimetry and normalized to metabolic mass estimated by dual-energy X-ray absorptiometry. A 10% loss in body weight in weight-reduced rats was accompanied by a 15% suppression in adjusted REE. This enhancement in metabolic efficiency was not altered with either 8 or 16 wk of weight maintenance, but it did resolve when the forced control of intake was removed and the weight was regained. The rate of weight regain increased with the time in weight maintenance and was exceptionally high early during the relapse period. During this high rate of weight gain, the suppression in REE persists while consumption increases to a level that is higher than when they were obese. In summary, an enhanced metabolic efficiency and an elevated appetite both contribute (60% and 40%, respectively) to a large potential energy imbalance that, when the forcible control of energy intake is relieved, becomes actualized and results in an exceptionally high rate of weight regain.