Objective To observe the efficacy and safety of carbon dioxide (CO2) fractional laser combined with autologous fat injection in patients with facial depressed scar. Methods Sixty patients with facial depressed scar plastic surgery admitted to Wenzhou Panhealth Medical Canter from January 2022 to June 2023 were randomly divided into control group and observation group, with 30 patients in each group. The control group was treated with CO2 fractional laser, and the observation group was treated with autologous fat injection. The clinical efficacy, scar improvement and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 93.33%, which was higher than 70.00% in the control group (P <0.05). After treatment, the scores of color, vascular distribution, thickness and softness in the two groups were lower than those before treatment, and those in the observation group were lower than the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion CO2 fractional laser combined with autologous fat injection can improve the scar symptoms of patients with facial depressed scar without increasing adverse reactions, and the effect is reliable.