If polymer electrolyte water electrolysis (PEWE) is to penetrate the energy market in the context of power-to-x, challenges related to component durability need to be understood and addressed. In this study, PEWE component degradation mechanisms are induced by combining catalyst-coated membranes (CCMs) with specific cell materials and operating conditions. The effect of the cell compression on the catalyst layer performance is investigated using cell assemblies with porous transport layers (PTLs) having different material properties. Rigid PTL-surface features result in local variation in anode catalyst layer (CL) porosity, and increased CL proton transport resistance. The creep of the CCM leads to the formation of thin sections and an increase in the content of H2 in the O2 product gas, causing in turn higher fluoride release rate from the ionomer/membrane. In addition, PEWE cells are subjected to a start-stop protocol to promote catalyst degradation through the formation of active, but unstable iridium hydroxo species. An increasing trend of catalyst dissolution is observed in the case of CCM samples that were operated at higher potential.