Carbon dioxide (CO2) flooding has been applied extensively worldwide to improve oil recovery from hydrocarbon reservoirs. One of the main problems associated with CO2 flooding is asphaltene precipitation, which leads to pore plugging, and eventually, low oil recovery. Asphaltene precipitation during CO2 flooding has been extensively studied for conventional oil reservoirs, however, with recent applications of CO2 flooding in unconventional shale reservoirs, it is important to study asphaltene precipitation and mitigation in nano-sized pores. This research investigates the main factors that can affect asphaltene precipitation in nano-sized pores during CO2 flooding, and attempts to mitigate this precipitation using common asphaltene mitigation chemical agents. Filter membranes with 0.2, 10, and 100 nm pores size were used in this study. The factors impacting asphaltene precipitation studied include the CO2 injection pressure, using 200, 400, and 750 psi, the experimental vessel temperature, using 60, 100, and 150 °C, crude oil viscosity, including 470, 260, and 67 cp, CO2 soaking time using 0.5 and 2 hours, filter membrane thickness, including 0.2, 0.6, and 1 mm, and pore size heterogeneity by combining different pore sized filter membranes together. The mitigation chemicals used include kerosene, xylene, naphtha, heptane, and water. The asphaltene wt% for both the produced oil and the bypassed, unproduced, oil was measured for all experiments. Compared to the pure crude oil, not used in any experiment, the asphaltene wt% for the produced oil in all experiments was lower, while the asphaltene wt% for the bypassed oil was higher. The wt% of the asphaltene decreased with the increase in pressure due to the oil being forced out of the nano pores, while an increase in temperature resulted in an increase in asphaltene due to the higher temperatures resulting in instability of the asphaltenes in the oil. The higher viscosity oil had a higher asphaltene wt% in all experiments. Decreasing the CO2 soaking time reduced the asphaltene precipitation. The 100 nm pore size had an asphaltene wt% close to that of the normal crude oil. For the mitigation experiments, xylene and kerosene proved the best, while naphtha and heptane facilitated the precipitation of asphaltene. Pore plugging in conventional oil reservoirs is considered a large problem, and so it is considered extremely drastic if it occurs in the nan-sized pores of shale reservoirs. This research shows the main parameters that will impact asphaltene precipitation during CO2 flooding and illustrates the most effective chemical agent, form the ones applied in the study, to mitigate this precipitation.