A CeO2-WO3/TiO2-SiO2 catalyst was employed to investigate the poisoning mechanisms of Pb and SO2 during selective catalytic reduction (SCR). The introduction of Pb and SO2 suppressed the catalytic performance by decreasing the numbers of surface acid and redox sites. Specifically, Pb preferentially bonded with amorphous WO3 species rather than with CeO2, decreasing the numbers of both Lewis and Brønsted acid sites but exerting less influence on the reducibility. SO2 preferentially bonded with CeO2 as sulfate species rather than with WO3, leading to a significant decrease in reducibility and the loss of surface active oxygen groups. Although SO2 provided additional Brønsted acid sites via the interaction of SO42- and CeO2, it had little positive effect on catalytic activity. A synergistic deactivation effect of Pb and SO42- on CeO2 was found. Pb covered portions of the weakly bonded catalyst sites poisoned by SO42-, which increased the decomposition temperature of the sulfate species on the catalyst.