A mathematical model with a consideration of energy spilling is developed to describe the activated sludge in the presence of different levels of metabolic uncouplers. The consumption of substrate and oxygen via energy spilling process is modeled with a Monod term, which is dependent on substrate and inhibitor. The sensitivity of the developed model is analyzed. Three parameters, maximum specific growth rate (mu (max)), energy spilling coefficient (q (max)), and sludge yield coefficient (Y (H)) are estimated with experimental data of different studies. The values of mu (max), q (max), and Y (H) are found to be 6.72 day(-1), 5.52 day(-1), and 0.60 mg COD mg(-1) COD for 2, 4-dinitrophenol and 7.20 day(-1), 1.58 day(-1), and 0.62 mg COD mg(-1) COD for 2, 4-dichlorophenol. Substrate degradation and sludge yield could be predicted with this model. The activated sludge process in the presence of uncouplers that is described more reasonably by the new model with a consideration of energy spilling. The effects of uncouplers on substrate consumption inhibition and excess sludge reduction in activated sludge are quantified with this model.