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 (λ =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, 15μs, 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.