Uneven pressure drops in a 75-cell 9.5-kWe proton exchange membrane fuel cell stack with a U-shaped flow configuration have been shown to cause localised flooding. Condensed water then leads to localised cell heating, resulting in reduced membrane durability. Upon purging of the anode manifold, the resulting mechanical strain on the membrane can lead to the formation of a pin-hole/membrane crack and a rapid decrease in open circuit voltage due to gas crossover. This failure has the potential to cascade to neighbouring cells due to the bipolar plate coupling and the current density heterogeneities arising from the pin-hole/membrane crack. Reintroduction of hydrogen after failure results in cell voltage loss propagating from the pin-hole/membrane crack location due to reactant crossover from the anode to the cathode, given that the anode pressure is higher than the cathode pressure. Through these observations, it is recommended that purging is avoided when the onset of flooding is observed to prevent irreparable damage to the stack.