During the operation of high-power proton exchange membrane (PEM) fuel cell, huge heat is generated in the chemical reaction, which need be removed by efficient cooling design. To solve the problem of local overheating during PEMFC, a novel multi-input and output (MIMO) cooling flow field is proposed. The maximum temperature, temperature uniformity and pressure drop characteristics of the U-shaped and Z-shaped cooling flow fields with different MIMO channels configurations are researched by computational fluid dynamics (CFD) method. The results demonstrate that comparing with U-shaped cooling flow field, Z-shaped design can provide better temperature distribution with the same MIMO channel configuration. Moreover, the serpentine cooling flow field provides better cooling performance than parallel cooling flow field, but leads to higher pressure loss. Compared to other cases, Z-shaped serpentine MIMO channel presents the best cooling performance, reducing the maximum temperature value to 322.7 K.