Diesel engines, fuels, and aftertreatment systems have to be optimized together to meet the targets imposed in the engine and vehicle emissions regulations, especially for particulate matter (PM) and nitrogen oxides (NOx), Hydrocarbon-selective catalytic reduction (HC-SCR) over Ag/Al2O3 catalysts is in attractive, cost-effective choice for reducing NO,, especially in the presence of hydrogen, which can be produced on-board in a fuel reformer. However, at low temperatures, the Ag/Al2O3 SCR catalyst activity decays rapidly, indicating a time period of activity loss. In this work, the catalyst deactivation process has been studied using a thermogravimetric analyzer (TGA). The effect of the space velocity, hydrogen addition, and the engine exhaust from the engine operation on gas-to-liquid (GTL), rapeseed methyl ester (RME), and ultra-low sulfur diesel (ULSD) fuels at different operating modes was investigated. In addition, the presence of a prototype oxidation catalyst located in-between the engine out and the SCR catalyst was studied, and its effect on the SCR performance was addressed. Results from the TGA confirm that the accumulation of species on the catalysts is more accentuated at low load. Fueling the engine with GTL fuel can reduce the deposition of poisoning species (i.e., carbonitrates and soot) on the catalyst surface in the less favorable conditions (low temperature and low load). The incorporation of the prototype catalyst in front of the SCR catalyst, although it improved the NOx reduction reaction over the Ag/Al2O3 catalyst, did not significantly alter the deposition of possible poisoning species on the catalyst surface. Similarly, the hydrogen addition in the exhaust gas upstream from the SCR catalyst improved the NOx reduction without significantly affecting the deposition of such species on the catalyst.