Objective To explore the application value of ultra-thin split-thickness skin graft combined with CO2 fractional laser in patients with deep second degree burn wound. Methods A total of 82 patients with deep second degree burn wound admitted to our hospital from January 2022 to January 2024 were selected as the research subjects, and they were divided into the control group and the observation group by the random number table method, with 41 patients in each group. The control group was treated with ultra-thin split-thickness skin graft alone, and the observation group was treated with ultra-thin split-thickness skin graft combined with CO2 fractional laser. The ECCA score, rehabilitation indicators, stress disorder and complications were compared between the two groups. Results After 2 and 3 treatment sessions, the ECCA score of the observation group was lower than that of the control group (P <0.05). The wound erythema duration time, healing time and hospitalization time of the observation group were shorter than those of the control group, and the VAS score was lower than that of the control group (P <0.05). The scores of avoidance/ numbing symptoms, increased alertness symptoms and re-experiencing symptoms in the observation group after treatment were lower than those in the control group (P <0.05). The incidence of complications in the observation group (4.88%) was lower than that in the control group (21.95%) (P <0.05). Conclusion The application of ultra-thin split-thickness skin graft combined with CO2 fractional laser in the treatment of deep second degree burn wound can improve the recovery effect and scar recovery, reduce the degree of post-traumatic stress disorder, and has high treatment safety, which is worthy of clinical application.