Polymer Electrolyte Membrane Direct Ethanol Fuel Cells (PEM-DEFC) offer the possibility of a carbon-neutral, easily-handled small-scale power source but suffer from disadvantages such as high anode over-potentials and fuel cross-over. In the present work, a comprehensive one-dimensional, single phase, isothermal mathematical model is developed for a liquid-feed PEM-DEFC, taking into account all the necessary mass transport and electrochemical phenomena on both the anode side and the cathode side. Tafel kinetics expressions (with appropriate kinetic data taken from the literature) have been used to describe the electrochemical oxidation of ethanol at the anode and the simultaneous ethanol oxidation and oxygen reduction reaction at the cathode. The model fully accounts for the mixed potential effect caused by ethanol cross-over at the cathode and is validated using the data from the literature. Model predictions over a range of operating conditions show that ethanol cross-over can cause a significant loss of fuel in terms of production of electricity. Under optimized conditions, it is shown that a PEM-DEFC can be operated at a current density of 0.3 A cm-2 with a power density of 0.1 W cm-2 with a fuel utilization factor of about 90%. © 2011, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.