Objective To explore the effect of ultrapulsed CO2 fractional laser on skin barrier function in patients with depressed acne scar. Methods A total of 122 patients with depressed acne scar admitted to the Department of Dermatology, Luotian County Psychiatric Hospital from January 2022 to June 2024 were selected, and they were divided into the control group and the study group by the random number table method, with 61 patients in each group. The control group was treated with Nd:YAG laser, and the study group was treated with ultrapulsed CO2 fractional laser. The wound recovery time, skin barrier function, inffammatory factor levels, clinical efficacy and adverse reaction rate were compared between the two groups. Results The erythema duration, decrustation time and PIH time in the study group were shorter than those in the control group (P<0.05). After treatment, the sebum content and TWEL in the study group were lower than those in the control group, and the skin moisture content was higher than that in the control group (P<0.05). The levels of IL-1β and TNF-α in the study group after treatment were lower than those in the control group (P<0.05). The total effective rate of the study group (93.44%) was higher than that of the control group (73.77%) (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Ultrapulsed CO2 fractional laser shows superior treatment effect. It can accelerate wound healing, improve skin barrier function and aesthetics, effectively reduce inffammatory response, and has good safety.