The effects of cation exchange on methanol oxidation and dehydration by supported H3PMo12O40 catalysts were investigated by exchanging polyoxometalate (POM) protons with cations such as Na+, Me2+, Cu2+, and Al3+. The activity decreased dramatically for both oxidation and dehydration pathways with cation addition. The measured oxidation and dehydration turnover frequencies over Na-, Mg-, and Cu-exchanged POMs were primarily a function of the H+/POM ratio of the catalysts, and differences in the charge of the exchanged cations had little impact. Similar behavior with cation exchange was also observed for ethanol dehydration and oxidation. This study suggests that there are limited benefits of cation-exchanging supported POMs for reactions under mild conditions because changes to POM reducibility induced by cation exchange were not catalytically relevant, and decreasing the number and strength of acid sites crucial to selective oxidation and dehydration catalysis decreases the activity under these conditions.