Microbial fuel cells (MFCs) have recently achieved energy-positive wastewater treatment at pilot scale. Despite these achievements, there is still a limited understanding as to whether all wastewaters contain sufficient amounts of energy and, if so, whether MFCs can capture a sufficient amount of energy to offset electrical energy requirements in the wastewater treatment process. Currently, there are no tools or methods available that can determine whether an MFC can be energy-neutral a priori. To address this, we derived a simple relationship by setting the electrical energy requirements of a wastewater treatment facility equal to the net energy output of the MFC, such that the resulting expression describes the minimum chemical oxygen demand (COD) removal needed to achieve energy-neutral treatment. The resulting equation is simply a function of electrical energy requirements, Coulombic Efficiency, and cell voltage. This work provides the first ever quantitative method for determining if the MFCs are feasible to achieve energy-neutral treatment for a given wastewater and what level of performance is needed.