Copper stearate was applied as a catalyst for the oxidation of heavy oils. The catalytic effect was investigated by high-pressure differential scanning calorimetry (HP-DSC) and accelerating rate calorimetry (ARC). The results showed that copper stearate significantly improved the oxidation performance including decreasing activation energies, enhancing combustion efficiency of coke, and reducing induction time and ignition temperature. CuO nanoparticles were in-situ formed due to the decomposition of copper stearate. To understand the catalytic mechanism, the catalytic effect of copper stearate was compared with nickel stearate, iron stearate and CuO. Furthermore, the existed form and transition of copper stearate during the oxidation process of crude oil were investigated using thermogravimetric analyser coupled with FTIR-spectrometer (TG-FTIR), HP-DSC, X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The results indicated that copper stearate and in-situ formed CuO nanoparticles played their catalytic roles as a homogeneous and heterogenous catalyst in low and high-temperature ranges, respectively. It was believed that the high catalytic activity of CuO can be not only attributed to those well-known catalytic mechanisms, but also benefits from the well-distribution of both copper stearate and in-situ formed CuO nanoparticles.