A study of the microstructural differences between exfoliated and non-exfoliated MoS2-based materials is presented, relating them to differences in their catalytic activity. Both commercial (crystalline) MoS2 and molybdenum sulfide catalysts prepared by thiosalt decomposition are subjected to chemical exfoliation reported to separate MoS2 monolayers from the original structure. Electron microscopy results show that the chemical treatment yields non-typical MoS2 nanostructures. Average surface area is also modified by exfoliation. The thiophene HDS activity of commercial MoS2 increases after exfoliation, while it decreases after exfoliation in the case of MoS2 catalysts.