The effect of the sulfation of zirconia catalysts on their structure, acidity/basicity, and catalytic activity/selectivity toward the ketonization of organic acids is investigated by a combined experimental and computational method. Here, we show that, upon sulfation, zirconia catalysts exhibit a significant increase in their Brønsted and Lewis acid strength, whereas their Lewis basicity is significantly reduced. Such changes in the interplay between acid-base sites result in an improvement of the selectivity toward the ketonization process, although the measured conversion rates show a significant drop. We report a detailed DFT investigation of the putative surface species on sulfated zirconia, including the possible formation of dimeric pyrosulfate (S2O72-) species. Our results show that the formation of such a dimeric system is an endothermic process, with energy barriers ranging between 60.0 and 70.0 kcal mol-1, and which is likely to occur only at high SO42- coverages (4 S/nm2), high temperatures, and dehydrating conditions. Conversely, the formation of monomeric species is expected at lower SO42- coverages, mild temperatures, and in the presence of water, which are the usual conditions experienced during the chemical upgrading of biofuels.