CO2 fracturing is a critical technique for carbon capture, utilization, and storage (CCUS). It has a crucial role in oil-gas development and combating climate change. However, the high flow friction severely affects the fracturing construction. The micro-mechanism of CO2 vertical flow friction in fracturing pipe string is unclear, and it is difficult to experimentally simulate the fracturing conditions. Computational Fluid Dynamics model is used to investigate the micro-mechanism of CO2 flow friction in fracturing conditions to reduce friction. A turbulence model was optimized to accurately calculate the friction of CO2 pipe flow. Subsequently, the relationships between the velocity profile, friction factor, and thickness of viscous sublayer of pure CO2 and thickened CO2 were analysed in fracturing pipe string, wherein the temperature and pressure were in the range of 253.15–343.15 K and 10–60 MPa, respectively. In this paper, the micro-mechanism of CO2 flow friction in fracturing pipe string was revealed and the situation of thickened CO2 was additionally considered, since the effect of the thickener has generally been ignored in previous numerical investigations. The results demonstrated that a uniform velocity profile reduced the friction factor. The temperature and pressure changed the relationship between the thickness of viscous sublayer and roughness, which caused the variation in the friction factor of pure CO2 and thickened CO2. The effect of roughness height on flow was different in the viscous sublayer and turbulent core region. A method was proposed to reduce the friction by optimizing the CO2 thickener and changing flow temperature and pressure.