The permeability reduction associated with asphaltene precipitation and deposition in gas injection EOR processes has been widely observed and well-studied in conventional plays. In our previous research, such permeability reduction due to asphaltene deposition during gas huff and puff injection process in shale core plugs were observed. In this study, experiments were conducted to investigate the permeability reduction caused by asphaltene deposition in shale core samples during the CO2 huff and puff injection process. A dead oil sample from a Wolfcamp shale reservoir was used. A core scale simulation model was built up to mimic the huff and puff injection process in the experiment and the parameters for the asphaltene deposition in shale were obtained by matching the experimental oil recovery and permeability reduction data. The asphaltene precipitation and deposition process during the CO2 huff and puff injection experiment are discussed in details based on the simulation results. Experimental results showed that severe permeability damage was caused by asphaltene during CO2 huff and puff injection (e.g., 48.5%), especially in the first cycle (e.g., 26.8%). Analysis of the experiments using simulation approach show that oil recovery factor reduction starts right after the beginning of CO2 huff and puff injection and the effect of asphaltene deposition on oil recovery factor accumulated during the later cycles. The asphaltene deposition was mainly formed in the near surface area of the core plug. As the CO2 concentration is quickly increased in the first cycle and more oil is near the rock surface in the first cycle, asphaltene precipitation and deposition were most significant during the huff period in the first cycle compared with the subsequent cycles. In the puff period of the first cycle, asphaltene precipitation is quickly decreased, as CO2 flow back. In addition, although oil in the inner blocks continuously flows to the outer blocks during the puff period, due to the extremely low permeability of the core plug, the amount of oil is small and this oil has already experienced the asphaltene precipitation process during the previous huff period, very small amount of increase in the asphaltene deposition occurs during the subsequent puff periods.