The stability of Pt nanoparticles (NPs) supported on ultrathin SiO(2) films on Si(111) was investigated in situ under H(2) and O(2) (0.5 Torr) by high-pressure X-ray photoelectron spectroscopy (HP-XPS) and ex situ by atomic force microscopy (AFM). No indication of sintering was observed up to 600 °C in both reducing and oxidizing environments for size-selected Pt NPs synthesized by inverse micelle encapsulation. However, HP-XPS revealed a competing effect of volatile PtO(x) desorption from the Pt NPs (~2 and ~4 nm NP sizes) at temperatures above 450 °C in the presence of 0.5 Torr of O(2). Under oxidizing conditions, the entire NPs were oxidized, although with no indication of a PtO(2) phase, with XPS binding energies better matching PtO. The stability of catalytic NPs in hydrogenation and oxidation reactions is of great importance due to the strong structure sensitivity observed in a number of catalytic processes of industrial relevance. An optimum must be found between the maximization of the surface active sites and metal loading (i.e., minimization of the NP size), combined with the maximization of their stability, which, as it will be shown here, is strongly dependent on the reaction environment.