A mesoscale simulation is developed to simulate transport and electrochemistry in a small section of a proton exchange membrane fuel cell (PEMFC) cathode catalyst layer. Oxygen, proton, and electron transport are considered in the model. Many simulations are run with a wide variety of different parameters on stochastically reconstructed microstructures with a resolution of 2 nm. Knudsen diffusion plays an important role in limiting the transport of oxygen through the catalyst layer. Using larger carbon spheres in the catalyst layer increases the effective diffusivity of oxygen through the catalyst layer. The effective proton conductivity increases when larger spheres are used, a normal distribution of spheres is used, or a higher overlap tolerance is used. Increasing the overlap tolerance or overlap probability results in an increase in the effective electron conductivity. When electrochemical reactions are considered in a part of the catalyst layer that is close to the gas diffusion layer, the critical parameter that determines oxygen consumption is the carbon sphere radius. Oxygen consumption at a given carbon volume fraction is larger in microstructures containing spheres with smaller radii, because there is more surface area available for electrochemical reactions. (C) 2010 The Electrochemical Society. [DOI: 10.1149/1.3478207] All rights reserved.