Abstract A high-temperature proton exchange membrane fuel cell (HT-PEMFC) is a promising clean and effective technology for power generation because of its simplified water and heat management as well as high CO tolerance. Therefore, it could be possible to directly use a reformate gas for HT-PEMFC without the need for sophisticated purification processes. Due to the non-uniform of H2 and CO distributions within fuel cells, the stack design is one of the key factors to enhance the performance and efficiency of HT-PEMFC. In this study, a single HT-PEMFC stack is investigated by considering the CO poisoning effect. The mathematical model of HT-PEMFC based on the electrochemical reaction model coupled with the diffusion model of a gas diffusion layer and electrolyte film layer is used for simulation studies. At high fuel utilization, hydrogen is highly consumed and CO concentration increases, having a significant impact on cell performance. The multi-stack HT-PEMFC is designed to minimize the CO poisoning effect and to maximize its efficiency. The power output that is obtained from each cell stack is presented and the overall power output is compared with single cell stack. Effect of different flow patterns, i.e., co-current and counter-current flow, on the HT-PEMFC stack performance is also presented.