The low-temperature catalytic oxidation of heavy crude oil (Xinjiang Oilfield, China) was studied using three types of catalysts including oil-soluble, watersoluble, and dispersed catalysts. According to primary screening, oil-soluble catalysts, copper naphthenate and manganese naphthenate, are more attractive, and were selected to further investigate their catalytic performance in in situ upgrading of heavy oil. The heavy oil compositions and molecular structures were characterized by column chromatography, elemental analysis, and Fourier transform infrared spectrometry before and after reaction. An Arrhenius kinetics model was introduced to calculate the rheological activation energy of heavy oil from the viscosity– temperature characteristics. Results show that the two oil-soluble catalysts can crack part of heavy components into light components, decrease the heteroatom content, and achieve the transition of reaction mode from oxygen addition to bond scission. The calculated rheological activation energy of heavy oil from the fitted Arrhenius model is consistent with physical properties of heavy oil (oil viscosity and contents of heavy fractions). It is found that the temperature, oil composition, and internal molecular structures are the main factors affecting its flow ability. Oil-soluble catalyst-assisted air injection or air huff-n-puff injection is a promising in situ catalytic upgrading method for improving heavy oil recovery.