Through a fruitful collaboration between three academic laboratories and a proton-exchange membrane fuel cell (PEMFC) manufacturer, important insights into the origin of the cell voltage losses monitored during on-site 110-cell-PEMFC-stack long-term operation (12,860 h i.e. 1.5 years) were provided. The decline of electrical performance is heterogeneous at the stack and the membrane-electrode assembly (MEA) scales, as shown by the monitoring of individual cell voltages during the ageing process and segmented cell characterizations at the end-of-life. The long-term electrical performance losses were bridged to the degradation of the MEA constitutive materials. They mostly originate from the emergence of large size holes in the proton exchange membrane (PEM), which lead to detrimental hydrogen crossover. The hydrogen crossover in turn causes the formation of radical species that actively participate in the irreversible corrosion of the high surface area carbon support in the cathode region neighbouring the hole. The degradation of the carbon support further prevents the efficient access of the reactive gazes and the proper removal of the reaction products. Depending on the size of the hole in the membrane, the localized loss of electrical performance may extend to the whole MEA, and depreciate its global performance. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.