The accumulation of advanced glycation end products (AGEs) occurs in ageing and in many degenerative diseases as a final outcome of persistent oxidative stress on cells and organs. Environmental alterations taking place during early embryonic development can also lead to oxidative damage, reactive oxygen species (ROS) production, and AGE accumulation. Whether similar mechanisms act on somatic and embryonic stem cells (ESC) exposed to oxidative stress is not known; and therefore, the modelling of oxidative stress in vitro on human ESC has been the focus of this study. We compared changes in N ε -carboxymethyl-lysine (CML) advanced glycation end products and RAGE levels in hESC versus differentiated somatic cells exposed to H2O2 within the noncytotoxic range. Our data revealed that hESC accumulates CML and RAGE under oxidative stress conditions in different ways than somatic cells, being the accumulation of CML statistically significant only in somatic cells and, conversely, the RAGE increase exclusively appreciated in hESC. Then, following cardiac and neural differentiation, we observed a progressive removal of AGEs and at the same time an elevated activity of the 20S proteasome. We conclude that human ESCs constitute a unique model to study the consequence of an oxidative environment in the pluripotent cells of the embryo during the human preimplantation period.