Cobalt catalysts supported on a series of mesoporous SBA-15 materials isomorphically substituted with zirconium (Zr/Si atomic ratio = 1/20) with different pore sizes (5.7 nm, 7.8 nm, 11.6 nm, 17.6 nm) have been synthesized. The catalysts were characterized by transmission electron microscopy, 29Si solid state magic angle spinning (MAS) NMR, N2 adsorption-desorption measurements, X-ray powder diffraction, X-ray photoelectron spectroscopy, H2-temperature programmed reduction, H2-temperature programmed desorption and O2 titrations. The results indicated that larger pore size led to weaker interactions between cobalt and the supports which lowered the temperature of both reduction steps (Co3O4→CoO and CoO→Co0). The catalytic performances of the catalysts in Fischer-Tropsch synthesis (FTS) were tested in a fixed bed reactor. It was found that the FTS catalytic activity and product selectivity depended strongly on the pore size of the catalysts. The catalyst with a pore size of 7.8 nm showed the best FTS activity, and the catalyst with a pore size of 17.6 nm showed the highest selectivity to C12–C20 and C20+ hydrocarbons.