The activity of a 5-wt% Cu/CeO2-x catalyst during preferential CO oxidation in hydrogen-rich gas mixtures was studied in a microchannel reactor. The CO concentration dropped from 1 vol.% to 10 ppm at a selectivity of 60%, at a temperature of 190 °C, and a weight hour space velocity (WHSV) of 55,000 cm3 g-1 h-1. Both the CO concentration and the temperature increased when the WHSV was increased from 50,000 to 500,000 cm3 g-1 h-1. An increase of the O2 concentration from a 1.2 to 3 fold excess reduced the CO concentration to 10 ppm in a broad temperature interval of 50 °C at WHSVs up to 275,000 cm3 g-1 h-1. The preferential CO oxidation could be carried out at higher flow rates and at higher selectivities in the microchannel reactor compared to a fixed-bed flow reactor.