The aim of this in vitro study was to investigate the potential of CO2 laser (10.6 µm) associated with fluorides in inhibiting enamel erosion. Human enamel samples were divided into 9 groups: G1: eroded enamel , G2: APF gel, G3: AmF/NaF gel, G4: AmF/SnF2 solution, G5: CO2 laser ( =10.6 µm) + APF gel, G6: laser + AmF/NaF gel, G7: laser + AmF/Sn F2 solution, G8: laser and G9: sound enamel. The CO2 laser parameters were: 0.45J/cm2, 15mis, 128Hz. After surface treatment, samples (except group G9) were immersed in 1% citric acid (pH 4.0, 3min). Knoop Surface microhardness (SMH) (0.49N, 20s) was measured at baseline and after surface softening. Data were statistically analyzed by ANOVA with subsequent pairwise comparisons (p 0.05). It was concluded that AmF/NaF and APF application have shown a potential to protect and control erosion progression in dental enamel and that CO2 laser irradiation at 0.45J/cm2 did not influence its efficacy. Solely CO2 laser at the same conditions may also significantly decrease enamel erosive mineral loss, although at lower levels.