Abstract The mechanical response of fuel cell proton exchange membranes subjected to a single hygro-thermal duty cycle in a fuel cell assembly is investigated through numerical means. To this end, the behavior of the membrane with temperature and humidity dependent material properties is simulated under temperature and humidity loading and unloading conditions. The stress-evolution during a simplified operating cycle is determined using finite element analysis for two clamping methods and two alignments of the bipolar plates. It is shown that compressive, plastic deformation occurs during the hygro-thermal loading, resulting in tensile residual stresses after unloading. These residual in-plane stresses in the membrane may explain the occurrence of cracks and pinholes in the membrane under cyclic loading.