In this study, mixed oxides of Mn-Cu and Fe-Cu on OMS-2 support having an octahedral structure were synthesized by the refluxing and impregnation methods. The characteristics of the materials were analyzed by XRD, FTIR, SEM, EDX, and H2-TPR. In the CO oxidation test, CuFeOx/OMS-2 had slightly higher catalytic activity but is significantly more stable than CuMnOx/OMS-2 and CuO/OMS-2. Due to its lower reduction temperature in H2-TPR analysis, the Mars-Van-Krevelen mechanism for CuFeOx/OMS-2 (Cu2+–O–Fe3+ ↔ Cu+–□–Fe2+) could take place more energetically than CuO/OMS-2 and CuMnOx/OMS-2 (Cu2+–O2−–Mn4+ ↔ Cu+–□–Mn3+). In addition, the interaction between Fe and Cu in the catalyst could improve the durability of the surface oxides structure in comparison with that between Mn and Cu. With the high specific rate and TOF of 28.6 mmol/h.g and 0.508, respectively, CuFeOx/OMS-2 has a great potential as an effective catalyst for low-temperature oxidation application in CO and possible VOCs removal.