Nature of the arsenic oxide surface modification during the XPS analysis. Display omitted •Arsenic oxide is photoreduced under standard XPS measurements.•Photoreduction involves oxygen desorption from the oxide surface.•Carbon contamination plays an important role in degradation.•Long X-ray exposures combined with long vacuum times should be avoided. XPS is extensively used for the characterization of arsenic-containing compounds like As(V) oxides, which can be found on the surface of minerals and important functional materials such as semiconductors and catalysts. However, potential sample degradation could alter the results. In this study, we explore the nature and extent of As2O5.5/3H2O phase degradation under XPS measurements in order to assess the intrinsic impact of this spectroscopic technique on the collected data. A series of experiments were designed for unravelling the effect of several factors like X-ray. irradiation time and intensity, vacuum time and charge compensation system. The influence of the structure and composition of the oxide was tested by taking the As2O5 phase as reference. Analyses were based on curve fitting of As3d, C1s and O1s high-resolution spectra, including survey quantification. Results show that degradation involves reduction of As(V) to As(III) species along with oxygen lost from the oxide lattice. As(V) photoreduction becomes extensive by repeating doses of X-ray irradiation; the photon beam intensity plays a major role in degradation, especially combined with the use of a dual flood gun as charge compensation system, while longer vacuum times also favor reduction. The dehydrated phase is more resistant to degradation likely due to a broader valence-band width. The presence of organic molecules from carbon contamination seems to play an important role in degradation. The possible underlying mechanism based on Auger decay of the initial core hole is considered. Minimal sample damage can be obtained by fixing the operating power and the vacuum and irradiation times at the least affordable values.