A cyclic open circuit voltage (COCV) accelerated stress test (AST) is designed to screen the simultaneous effect of chemical and mechanical membrane degradation in polymer electrolyte fuel cells. The AST consists of a steady state OCV phase to accelerate chemical degradation and periodic wet/dry cycles to provide mechanical degradation. The membrane degradation process induced by COCV AST operation is analyzed using a standard MEA with PFSA ionomer membrane. The OCV shows an initially mild decay rate followed by a higher decay rate in the later stages of the experiment. Membrane failure, defined by a threshold convective hydrogen leak rate, is obtained after 160 h of operation. Uniform membrane thinning is observed with pinhole formation being the primary cause of failure. Mechanical tensile tests reveal that the membrane becomes stiffer and more brittle during AST operation, which contributes to mechanical failure upon cyclic humidity induced stress. Solid state ¹⁹F NMR spectroscopy and fluoride emission measurements demonstrate fluorine loss from both side chain and main chain upon membrane exposure to high temperature and low humidity OCV condition.