The effect of exposure to ambient air of MoS₂-based, γ-Al₂O₃-supported, hydrodesulfurization (HDS) catalysts has been studied using high-resolution transmission electron microscopy (HRTEM). Analysis of unpromoted as well as Ni- and Co-promoted MoS₂ samples showed that the number of MoS₂ slabs and the average slab length decreased as a function of air exposure time. A parallel X-ray photoelectron spectroscopy (XPS) study showed this effect to be due to oxidation. During the first 24 h of exposure to air, all 1 bar sulfided (Ni/Co)MoS₂ samples showed an initial slab length decrease of approximately 20%. After an additional month in air, the slabs had deteriorated significantly further. A sample of CoMoS₂ sulfided at 30 bar showed a slightly enhanced effect of oxidation, particularly after the first 5 min in air. The combined HRTEM and XPS results lead to the proposal of the formation of a protective oxide ring around the remaining sulfidic species inside the MoS₂ slabs to explain the mechanism of this oxidation process. The data obtained in this study emphasize the general necessity of shielding vulnerable catalyst samples from air during preparation and characterization, a message relevant in all fields of research related to catalysis.