Water and oxygenated compounds are generally viewed as highly detrimental to the stability of sulfided hydrotreating catalysts. In this paper, a sulfided NiMo/gamma-Al2O3 catalyst was treated in a batch reactor under typical hydrotreating conditions with or without water vapor. Changes of the HDO activity, composition, and texture of the various catalyst samples were further evaluated. Catalyst samples used in the HDO of organic oxygenated compounds were also characterized by XPS for modifications of the chemical surface composition. Water caused a decrease of the catalytic activity to one-third the activity of the fresh catalyst but did not change the hydrogenation-hydrogenolysis selectivity. Water was also the cause of a small loss of the specific surface area conjugated to some crystallization of the gamma-alumina support in a hydrated boehmite phase. On the other hand, the metal content, the dispersion, and the sulfidation state were not specifically affected by water. The deactivation would rather be related to the appearance of oxidized nickel species. The observations can be interpreted as resulting from the formation of an inactive nickel sulfate layer covering the active sulfide phases or from the formation of nickel aluminate. Otherwise, the oxidation of the molybdenum sulfide phase by water or oxygenated compounds in reaction conditions is very limited.