Organic-rich shale reservoirs are rich in reductive minerals, such as pyrite and other organic matters. The working fluid for the development of shale gas reservoirs contains large amount of dissolved oxygen. Once the working fluid enters the organic shale reservoir, it will oxidize the reducing components, cause mineral transformation, release solid phase particles, change the pore structures, and damage the seepage capacity of organic-rich shale reservoirs. The understanding and evaluation of the oxidation sensitivity is of great significance for improving the productivity of shale reservoirs. Therefore, organic shale of the Longmaxi Formation in the Pengshui area of the southeastern Sichuan Basin (China) was taken as the research object in the current work. In order to evaluate the reservoir fluid sensitivity, experiments were conducted to evaluate the oxidation sensitivity of the organic-rich shale reservoir. The experimental results showed that oxic fluids had the highest degree of damage on the permeability of shale than the reductive and degassed fluids. The oxidation sensitivity indices, Sox, of the shale samples were found to be 65.62% and 54.88%, respectively, which are moderately strong. The mechanism for the damage of the oxidation sensitivity of shale involves the production of Fe2O3, Fe(OH)(3), FeCO3 (siderite), CaSO4 center dot 2H(2)O (dihydrate gypsum), MgSO4, other precipitated solid particles (chemicals), and the shale debris. Therefore, the pores and fractures were blocked by solid particles, resulting in the decrease in fracture width as well as the number of solid particles, which could be expelled. An appropriate concentration of oxidants has a positive effect on the permeability of organic-rich shale. The oxidation will produce macroscopic cracks and a large number of dissolution pores that significantly improved the transport capacity of the pore fracture system, and increased the permeability of the organic-rich shale.