A nano-scale understanding of the degradation mechanisms responsible for the performance loss of high surface area (HSA) catalysts implemented in polymer electrolyte membrane fuel cells (PEMFC) is essential for the development of improved catalysts. Here we present a systematic study of the degradation mechanisms of a HSA carbon supported Pt (Pt/C) catalyst. By monitoring the electrochemical surface area (ECSA) loss under accelerated stress test (AST) protocols with identical location transmission electron microscopy (IL-TEM), it is shown that different degradation mechanisms are responsible of the performance loss of Pt/C depending on the applied AST protocol. Three different AST protocols have been applied, i.e. i) load cycles between 0.6-1.0 V-RHE, ii) start/stop cycles between 1.0-1.5 V-RHE, and iii) a treatment consisting of a mix of both conditions (cycling between 0.4-1.4 V-RHE). During load cycles the main degradation mechanisms are nanoparticle (NP) migration as well as Pt dissolution and re-deposition. However, after applying start/stop cycles only NP detachment from the carbon support is detect, whereas the third AST protocol induces all degradation modes concomitantly. (C) 2013 The Electrochemical Society. All rights reserved.