Vanadium-doped acid prepared mesoporous spheres (V-APMS) were prepared with vanadium loadings of 1–40 wt% using a wet-impregnation method. The effects of vanadium loading on the support were studied using N2 physisorption and powder XRD. The pore volumes, surface areas, and pore diameters of the catalysts decreased as a function of vanadium loading and diffraction peaks corresponding to crystalline V2O5 were detected by XRD at an intermediate V loading, becoming more intense as the V content increased. These results indicate that at low V loadings, the vanadium oxide species were well-dispersed on the silica; however, at higher V loadings crystalline V2O5 was formed within the pores of the APMS. V-APMS was then studied as a heterogeneous catalyst for the oxidation of the chemical warfare agent stimulant 2-chloroethyl ethyl sulfide (CEES) using tert-butyl hydroperoxide (TBHP) as the oxidant. Kinetic studies at temperatures ranging from 0 to 50 °C showed that materials with low V loadings were the most effective catalysts for the reaction. The mechanism of the oxidation reaction appeared to be different for catalysts that were composed of well-dispersed vanadium oxide species than for catalysts containing microcrystalline or crystalline V2O5. Finally, a possible reaction scheme for the oxidation of CEES by V-APMS is discussed.