A biological setpoint for fatness has been proposed in the medical literature. This body weight setpoint functions as a point of stable equilibrium. In an underfed state, with resulting weight loss, the body will reduce the relative energy expenditure by metabolic adaption which reduces the rate of weight loss. Previous mathematical models of energy expenditure and weight loss dynamics have not addressed this setpoint mechanism. The setpoint model has been proposed to quantify this biological process and is unique in predicting energy expenditure during weight loss as a function of the setpoint fat-free mass ratio and setpoint energy expenditure, eliminating the various controlling characteristics such as age, gender and heredity. The model is applied to the seminal Minnesota human semistarvation experiment and is used to predict weight vs time on an individual basis and the caloric requirements for weight maintenance at the reduced weight. Comparison is made with the Harris-Benedict equations and the Brody-Kleiber (W3/4) law.