The electrochemical reaction inside a high-power fuel cell generates a lot of heat. Excessive heat affects the performance of the membrane, so it is necessary to introduce coolant. The main objective of coolant is regulating the temperature of relatively high-power proton exchange membrane fuel cell (PEMFC) stacks efficiently. The coolant channel has a great influence on the performance of PEMFC. In this work, a multiphase, 3D PEMFC model with serpentine flow channel is developed. In order to rank structural parameters according to the degree of influence on fuel cell performance, this study analyzed the current density, O2 mass fraction, and the distributions of temperature based on an orthogonal test scheme with three factors and three levels. The results show that rib width between the reactant flow channel and the cooling channel has the greatest influence on the current density, and gas flow channel width has the least influence.