Altering the structure of the enamel surface around the orthodontic bracket by reducing its content of carbonate and phosphate resulting from application of CO(2) laser may represent a more effective strategy in preventing caries in this region. This study aimed at determining whether irradiation with a CO(2) laser combined with fluoride-releasing bonding material could reduce enamel demineralization around orthodontic brackets subjected to cariogenic challenge. Ninety bovine enamel slabs were divided into five groups (n = 18): non-inoculated brain-heart infusion broth group, non-fluoride-releasing composite resin (NFRCR-control group), resin-modified glass ionomer cement (RMGIC), CO(2) laser + Transbond (L+NFRCR) and CO(2) laser + Fuji (L+RMGIC). Slabs were submitted to a 5-day microbiological caries model. The Streptococcus mutans biofilm formed on the slabs was biochemically and microbiologically analysed, and the enamel Knoop hardness number (KHN) around the brackets was determined. The data were analysed by ANOVA and Tukey tests (α = 0.05). Biochemical and microbiological analyses of the biofilm revealed no statistically significant differences among the groups. Lased groups presented the highest KHN means, which statistically differed from NFRCR; however, no difference was found between these lased groups. RMGIC did not differ from NFRCR which presented the lowest KHN mean. The CO(2) laser (λ = 10.6 μm; 10.0 J/cm(2) per pulse) use with or without F-bonding materials was effective in inhibiting demineralization around orthodontic brackets. However, no additional effect was found when the enamel was treated with the combination of CO(2) laser and an F-releasing material.