Glucose oxidase (GOx) immobilization onto mesoporous SBA-15 silica and two mesocellular foams (MCF) characterized by similar surface area and pore volumes but different pore/cell dimensions was examined. The covalent grafting of the enzyme through amide bonds was evidenced by controlling pH conditions, thus preventing GOx leaching. The immobilized protein activity was found to be significantly higher for the mesocellular foam with both cells and windows size larger than the enzyme dimensions. The Michaelis–Menten parameter KM for the immobilized GOx was similar to that of the free enzyme. GOx exhibited higher thermal stability when immobilized on the mesocellular foam compared to the free enzyme. The activity decay of GOx in presence of water soluble organic solvents, i.e., acetonitrile or methanol, was studied. At 50 °C, half of the immobilized GOx activity could be retained in 40 v/v% MeOH/acetate buffer.