Objective To evaluate the effect of CO2 fractional laser combined with clindamycin phosphate gel on quality of life in patients with rosacea. Methods A total of 100 patients with rosacea admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from May 2025 to January 2026 were selected, and they were divided into the control group and the experimental group by the random number table method, with 50 patients in each group. The control group received topical clindamycin phosphate gel, and the experimental group received CO2 fractional laser on the basis of the control group. The clinical efffcacy, skin lesion status, demodex folliculorum count, quality of life, adverse reaction rate and recurrence rate were compared between the two groups. Results After 4 weeks of treatment, the total clinical effective rate of treatment in the experimental group was higher than that in the control group (P<0.05). After 2 and 4 weeks of treatment, the erythema score, papule and pustule score, demodex folliculorum count and Dermatology Life Quality Index (DLQI) score of the experimental group were lower than those of the control group (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). The recurrence rate of the experimental group at 3 months after treatment was lower than that of the control group (P<0.05). Conclusion Clindamycin phosphate gel combined with CO2 fractional laser has deffnite curative effect in the treatment of rosacea, with few adverse reactions and low recurrence rate, indicating that this therapeutic regimen is safe and effective.