Abstract: The study of reservoir rock damage induced by gas injection is of great significance to the design of reservoir stimulation and the improvement of oil and gas recovery. Based on an example horizontal well in the Hudson Oilfield of the Tarim Basin and considering the multi-physics coupling effects among high-pressure fluid, rock deformation, and damage propagation during CO2 injection, a three-dimensional finite element model for CO2 injection in deep reservoir considering seepage-stress-damage coupling was developed. The evolution of reservoir rock damage under different CO2 injection conditions was systematically investigated. The results show that tensile damage and shear damage are concentrated in the vertical direction and the horizontal maximum compressive principal stress direction, respectively, and the tensile damage is the main damage mode. At higher CO2 injection rate and pressure, the damaged areas near the wellbore are mainly distributed in the direction of the maximum compressive principal stress, and the development of the damaged area near the wellbore will be inhibited by the formation and evolution of far-field damage. CO2 injection aggravates the extension of tensile damage, but inhibits the initiation of shear damage, and eventually leads to the gradual transition from shear damage to tensile damage. Under the same injection conditions, CO2 injection has superior performance in creating rock damage compared with the injection of nitrogen and water. The results in this study provide guidance for enhanced oil recovery in deep oil and gas reservoirs with CO2 injection.