The mechanical compression used in the construction of PEFCs improves effective current collection and gas sealing, however it results in structural deformation of the MEA, affecting reactant transport with adverse consequences for the electrochemical performance of the cell. The present study uses X-ray CT to characterise MEA under compression and determine effective properties of the porous domain. The comprehensive modelling approach couples a structural model of the MEA under compression to a multi-phase, non-isothermal electrochemical performance model. Liquid water saturation in the cathode domain that promotes mass transport losses is validated with neutron radiography. Here, the structural model considers the fuel cell stacking process at three compressions and highlights the non-uniform distribution of porosity and effective properties under non-uniform cell compression, affecting localised current distribution and water transport. An increase in compression showed a negligible effect on the performance in the activation region, the performance was marginally improved in the ohmic region and significantly affected in mass transport region, promoting cell flooding. The non-uniform compression effects are found to be important considerations for robust modelling studies as it increases the nonuniformity in localised current, temperature and flooding that would further alter the durability of the fuel cell.