Accelerated deactivation, caused by thermal aging (TA) and/or sulfur+water poisoning (SW), of the PtPd/γ-Al2O3 natural-gas oxidation catalyst was studied. Thermal aging and poisoning treatments were performed separately and with varied combinations and comprehensive characterization of the catalyst was carried out after each step. The fresh catalyst has small, oxidized PtPd particles (<5nm) uniformly distributed in the γ-alumina washcoat. After the SW-treatment, a small amount of bulk aluminum sulfate was observed near the slightly grown noble metal particles. During the thermal aging, γ-alumina changed to δ-/θ- and α-alumina. In addition, total decomposition of oxidized Pt and partly decomposition of oxidized Pd occurred resulting in the formation of the grown noble metal particles with a bimetallic PtPd core and a polycrystalline PdO shell. Also few, small (~5nm) bimetallic PtPd particles were still detected. In the TA+SW-treated catalyst with grown noble metal particles, a small amount of bulk aluminum sulfate was detected and it was randomly distributed over the noble metal particles and washcoat. The activity in the terms of methane conversion over the TA-, SW-, and SW+TA-treated catalysts was similar but it was decreased compared to the fresh catalyst. The activity of the TA+SW-treated catalyst was drastically decreased compared to the fresh catalyst due to significant morphological changes and aluminum sulfate formation.