Objective To analyze the effect of fractional CO2 laser combined with intense pulsed light on skin lesions in patients with post-acne scar. Methods A total of 62 patients with post-acne scar admitted to Xingyi People's Hospital from June 2024 to June 2025 were selected. According to the random number table method, they were divided into the control group and the observation group, with 31 patients in each group. The control group was treated with fractional CO2 laser, and the observation group was treated with fractional CO2 laser combined with intense pulsed light. The skin lesions, scar and erythema area, and aesthetic effect were compared between the two groups. Results After treatment, the scores of skin lesions, lesion number, lesion color and swelling-hardness degree in the observation group were lower than those in the control group (P<0.05). The scar area and erythema area in the observation group were smaller than those in the control group (P<0.05). The ECCA score and skin melanin index in the observation group were lower than those in the control group (P<0.05). Conclusion The application of fractional CO2 laser combined with intense pulsed light in patients with post-acne scar can effectively improve skin lesions, reduce scar and erythema area, and is conducive to enhancing aesthetic effect, which is worthy of clinical application.