In a typical proton exchange membrane fuel cell (PEMFC), Nafion, i.e. a typical proton-exchange membrane, allows to permeate hydrogen and oxygen to the opposite electrode, resulting in unexpected parasitic reaction, and reduces open circuit potential (OCP) because of undesirable potential mixing. This paper investigates the influences of the anode flooding and fuel starvation on cell performance under mixed-potential conditions. A two-dimensional computational fluid dynamics model was formulated by considering direct oxidation reaction when hydrogen and oxygen molecules meet to account additional water generation in both anode and cathode catalyst layers. The present model was validated by comparing the simulated cell polarization with experimentally measured cell polarization. The authors have prepared membrane electrode assembly by the decal transfer method to precisely determine various parameters that dominate the electrode kinetics. Model validation was also conducted to clearly present the predictability of the model with different cell configurations, i.e. with and without microporous layers. Through the model, effect of the oxygen permeation coefficient of the Nafion membrane on the anode flooding was investigated. In addition, reverse-current generation was predicted with different anode saturations and oxygen permeation coefficients to provide a detailed explanation on their relationship. Copyright (c) 2013 John Wiley & Sons, Ltd.