Chemical deactivation of Ag/Al2O3 catalysts due to aromatic species and sulfur present in the diesel fuel is a major challenge in hydrocarbon-based selective catalytic reduction (HC-SCR) of NOx from diesel engine exhaust. In this paper, mechanisms for catalyst deactivation due to both aromatic species and sulfur are investigated using model hydrocarbon species, such as toluene and xylene, as well as sulfation treatment. A number of experimental techniques, viz., microreactor studies, temperature programmed oxidation, temperature programmed decomposition, and diffuse reflectance UV-vis, are employed to understand the contribution of aromatic species and sulfur to catalyst deactivation. It is observed that the inhibition effect due to aromatic species is reversible, but is dependent on the size and concentration of the aromatic species. The sulfation effect is irreversible at a given temperature, and sulfur not only reacts with the silver particles, but also affects the relative magnitude of the different types of hydrocarbon species adsorbed on the catalyst surface, thereby changing the catalytic activity for the SCR chemistry.