INTRODUCTION: Burn scars can cause permanent disfiguring problems with limited treatments available. OBJECTIVES: To assess and correlate the clinical and histopathological effects of fractional CO2 laser on thermal burns in a controlled study. METHODS: Fifteen patients 11 with hypertrophic and four with keloidal scars received three CO2 fractional laser sessions every 4-6 weeks. Half of the scar was untreated as a control. Clinical evaluation by Vancouver, PSOAS scores, and photography before, monthly, and 3 months after the last laser session was performed. Ten patients were evaluated histopathologically by standard H&E, Masson trichrome, and Elastica von Gieson special stains. RESULTS: Hypertrophic scars (HTSs) showed textural improvement and a significant decrease of Vancouver, POSAS observer, and patient scores by the end of follow-up period in the laser-treated area (P = 0.011, 0.017 and 0.018, respectively) unlike keloidal scars. Histopathology revealed significant decrease in scar thickness in HTSs only (P < 0.001) as well as a significant decrease in collagen bundle thickness and density in the upper dermis in both types of scars. CONCLUSIONS: Fractional CO2 laser is a possible safe and effective modality for the treatment of hypertrophic burn scars with improvement achieved both clinically and histopathologically.