The structural changes induced in a silica-titania mixed-oxide support (1:1 molar ratio) by chlorine addition at different loading levels, their relation to the structural characteristics of supported MoOx species over the support, and their correlation with ethane oxidative dehydrogenation (ODH) activity have been examined. The molybdenum and chlorine precursors are incorporated into the Si/Ti support network as it forms during gelation by using a "one-pot" modified sol-gel/coprecipitation technique. In situ X-ray diffraction during calcination shows the Si/Ti 1:1 mixed-oxide support is in a state of nanodispersed anatase titania over amorphous silica. With the addition of molybdenum and chlorine modifier, this anatase feature becomes more pronounced, indicating a decreased dispersion of titania. The effective titania surface area on the chlorine-doped Si:Ti support obtained from 2-propanol temperature-programmed reaction supports this observation. Raman spectra of dehydrated samples point to an enhanced interaction of MoOx species with silica at the expense of titania. X-ray photoelectron spectroscopic results show that, without forming a molybdenum chloride, the presence of chlorine significantly alters the relative surface concentration of Si vs Ti, the electronic structure of the surface MoOx species, and the oxygen environment around supported MoOx species in the Si/Ti network. Secondary ion mass spectrometry detected the existence of SiCl fragments from the mass spectra, which provides molecular insight into the location of chlorine in Mo/Si:Ti catalysts. The observed increase in ethane ODH selectivity with chlorine modification may be ascribed to the MoOx species sharing more complex ligands with silica and titania with the indirect participation of chlorine. Steady-state isotopic transient kinetic analysis (SSITKA) is used to to examine the oxygen insertion and exchange mechanisms. The catalysts show very little oxygen exchange with the gas phase in the absence of a reaction medium. During the steady-state ODH reaction, lattice oxygen appears to be the primary source of oxygen in the formation of water and CO2.