The effect of exposure to ambient air of MoS2-based, -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 around 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 minutes 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.