A three-dimensional mathematical model of PEM fuel cell operated on reformate is developed based on our previous established fuel cell model (Zhou and Liu, 2001), by incorporating the adsorption and oxidation kinetics of CO on platinum surface proposed by Springer et al (1997, 2001). This model is capable of studying the effect of CO poisoning as well as the hydrogen dilution effect by inert gases. The adsorption and oxidation kinetics of CO on platinum surface are incorporated in the source terms of the species equations, thus basic form of the mathematical equations are the same as those used for PEM fuel cell operated on pure hydrogen. With this model, we can obtain detailed information on the CO poisoning and variation of CO and hydrogen concentrations inside the anode. The modeling results from this 3D model revealed many new phenomena that cannot be obtained from previous 1D or 2D models. The model can be used to provide guidance for anode design optimizations. In the paper, results of the effects of various operating and design parameters, such as anode flow rate, gas diffuser porosity, gas diffuser thickness, and the width of the collector plate shoulder, are also presented.