Here, we present a novel method to control the size of CuO nanoparticles (NPs) and Cu loading in SBA-15 via fast desorption of supercritical CO2 (scCO2). After calcination, the average size of the CuO NPs (6.47 ± 2.89∼2.18 ± 0.97 nm) decreased with the increase of the depressurization rate (20-14 MPa, 50 °C) from transmission electron microscopy, and the x-ray diffraction results also indicated the decrement of the average particle size (8.6∼4.3 nm by a Scherrer equation). Two reduction peaks situated at 195 °C and 220 °C were found from the temperature-programmed reductions with H2 profiles, and the intensity of the low-temperature peak increased with increasing the rate for a profile. The hydrogenation of dimethyl oxalate (DMO) to ethylene glycol (EG) was selected to evaluate the catalytic activity of the as-prepared sample. The reaction was conducted at p = 3.0 MPa, T = 200 °C, H2/DMO = 120, the weight hourly space velocity = 1.2 h-1, and the EG selectivity remained at about 90% for over 100 h. The fast desorption of scCO2 caused mechanical perturbations and crystallization of the adsorbed salt ions on the supports, decreasing the particle size and increasing Cu loading (8∼12 wt%).