PEM fuel cell is a promising alternative green power source for vehicular application. However, its performance, cost and durability are sensitively impacted by its sensitivity to impurities in both fuel and air streams. In this study, a multi-phase multi-dimensional model with carbon monoxide in the anode side has been developed. The present model includes flow channel, gas diffusion layer, catalyst layer, and polymer electrolyte membrane, considering carbon monoxide (CO) poisoning and oxygen bleeding in the fuel stream. The model equations, based on the conservation laws for mass, momentum, energy, and species, considered in a steady state, are solved by using Fluent software. The results of the effects of CO concentration, a series of 3D simulation in anode catalyst layer, as well as oxygen bleeding, are presented, which indicate that CO has a severe influence on the performance of PEM fuel cell. In particular, the degree of CO poisoning is strongly dependent on the local rate of electrochemical reaction in the anode catalyst layer. Since the reaction rate is three-dimensional, CO poisoning effect is stronger at the location of high reaction rate. Therefore, providing oxygen bleeding at the high reaction rate zone tends to be most effective to mitigate the CO poisoning. The transient system and the degree of effect of Platinum (Pt) alloy catalyst loading at the high reaction rate zone are left to future work.