Abstract The Fe-modified sepiolite-supported Mn–Cu mixed oxide (Cu x Mn y /Fe-Sep) catalysts were prepared using the co-precipitation method. These materials were characterized by means of the XRD, N 2 adsorption–desorption, XPS, H 2 -TPR, and O 2 -TPD techniques, and their catalytic activities for CO and ethyl acetate oxidation were evaluated. The results show that catalytic activities of the Cu x Mn y /Fe-Sep samples were higher than those of the Cu1/Fe-Sep and Mn2/Fe-Sep samples, and the Mn/Cu molar ratio had a distinct influence on catalytic activity of the sample. Among the Cu x Mn y /Fe-Sep and Cu1Mn2/Sep samples, Cu1Mn2/Fe-Sep performed the best for CO and ethyl acetate oxidation, showing the highest reaction rate and the lowest T 50 and T 90 of 4.4 × 10 − 6 mmol·g − 1 ·s − 1 , 110, and 140 °C for CO oxidation, and 1.9 × 10 − 6 mmol·g − 1 ·s − 1 , 170, and 210 °C for ethyl acetate oxidation, respectively. Moreover, the Cu1Mn2/Fe-Sep sample possessed the best low-temperature reducibility and the lowest temperature of oxygen desorption as well as the highest surface Mn 4 + /Mn 3 + and Cu 2 + /CuO atomic ratios. It is concluded that factors, such as the strong interaction between the Cu or Mn and the Fe-Sep support, good low-temperature reducibility, and good mobility of chemisorbed oxygen species, might account for the excellent catalytic activity of Cu1Mn2/Fe-Sep.