This paper reports on numerical investigations for a proton exchange membrane fuel cell stack using a CFD-based simulation tool. The stack simulation tool is constructed based on unit cells in parallel that have all components resolved and major transport equations solved in a two-dimensional configuration. The transport equations considered in the model are modified from a complete set of conservation equations (mass, momentum, energy, species and electrical potential). The stack tool also incorporates a flow network solution procedure for all gas and coolant channels to account for flow sharing of fluids at the stack level. The unit cell model in the 2D stack tool is validated with a 3D, comprehensive CFD model. The parameters used in the flow network model are calibrated from experimental data. The stack tool is used to determine the sensitivities of the baseline design of a stack with respect to design parameters, e.g. the dimensions of headers and unit cell components, and operating conditions such the oxidant stoichiometric ratio and coolant flow rate, and so on. Simulation results for the baseline stack with an anomalous unit cell (ill-behaving in flow, thermal or electrical transport) are presented to show how a stack's performance would deviate from the design point due to unfavorable conditions.