The use of sulfonic acid-functionalized heterogeneous catalysts in conjunction with the use of dimethyl sulfoxide (DMSO) as co-solvent in the catalytic transformation of fructose in ethanol to produce 5-ethoxymethyl furfural (EMF) is shown as an interesting alternative route for the production of this advanced biofuel. Arenesulfonic acid-modified SBA-15 mesostructured silica (Ar-SO3H-SBA-15) has been the most active catalyst, ascribing its higher catalytic performance to the combination of excellent textural properties, acid sites surface concentration and acid strength. Noticeably, DMSO promotes the formation of EMF and HMF, reducing the extent of side reactions. Reaction conditions (temperature, catalyst loading and DMSO concentration) where optimized for Ar-SO3H-SBA-15 via response surface methodology leading to a maximum EMF yield of 63.4% at 116 °C, 13.5 mol% catalyst loading based on starting fructose and 8.3 vol.% of DMSO in ethanol after 4 h of reaction. Catalyst was reused up to 4 consecutive times, without regeneration treatment, showing a slight gradual decay in activity attributed to the formation of organic deposits on the catalyst’s surface.