To enhance the low cycle stability of LiCoPO4, the development of stable separators in batteries is required, since they are oxidized in the high-voltage system at around 5 V, affecting the cycle performance of high-voltage lithium-ion batteries. The performance of the batteries also depends on the porous structure of separators. Here we report improved coulombic efficiency and capacity retention of LiCoPO4 by using a three-dimensionally ordered macroporous polyimide (3DOM PI) separator, compared with a conventional polypropylene separator with heterogeneous pore structure. The enhanced cycle stability of the cell using 3DOM PI separator is attributed to its ordered macroporous structure and high anodic stability. The uniform current distribution created by the ordered macroporous structure results in the low overpotential during charge process, preventing the oxidation of electrolyte and the growth of the resistive film on the cathode surface during cycling. Furthermore, the high anodic stability of 3DOM PI separator maintains its chemical and macroporous structures after cycling at high potentials, leading to the superior stability of the cell.