Identifying and quantifying the failure induced by start-up and shut-down (SU/SD) protocols of a Polymer Electrolyte Membrane fuel cell requires detailed understanding. Studies on SU/SD are difficult to compare as the tests are not conducted either at the same conditions or with the same materials. In this work, we used a common fuel cell testing hardware, test bench and materials to study the failure modes of three different SU/SD cycles. A faster rate of gas switching and load ramping accelerated the CL degradation in all three cycles. A cycle with load on/off showed higher degradation than a dummy load incorporated cycle after 550 cycles. However, the cycle where the load is ramped showed 3% mass transport over potential from its beginning-of-life. We applied the dummy load incorporated SU/SD cycle to a segmented membrane electrode assembly and observed the higher voltage losses at the exit segments of a segmented fuel cell. © The Electrochemical Society.