This study investigated the effect of surfactants associated with sodium fluoride (NaF) on enamel erosion prevention, using an erosion-remineralization in vitro model. Sodium lauryl sulfate (SLS), polysorbate 20 (P20), and cocoamidopropyl betaine (CAPB) were tested, at concentrations of 1.0 and 1.5%, and associated or not with NaF (275 ppm). The control groups were distilled water and the NaF solution. Bovine enamel samples (<i>n</i> = 12) were prepared and submitted to a 5-day cycling model: acid challenge (0.3% citric acid, pH 2.6, 4×/day), human saliva (2 h, 4×/day), and the treatment solutions (2 min, 2×/day). The protective potential of the agents against initial erosion was assessed by microhardness and the surface loss by profilometry. Enamel surface wettability was determined by goniometry, protein adsorption was measured by spectroscopy (FTIR), and the KOH-soluble fluoride was quantified. Goniometry showed that SLS and CAPB increased enamel wettability. No differences were found among the surfactants regarding protein adsorption. Microhardness showed that SLS reduced NaF protection. P20 (1 and 1.5%) and CAPB 1.5% presented a protective effect, but lower than the NaF solution. Profilometry showed that CAPB protected enamel, but no agent associated with NaF promoted a higher protection than the NaF solution alone. KOH-soluble fluoride analysis showed that all surfactants reduced the fluoride adsorption on the enamel surface. Therefore, the surfactants tested (except for P20) changed the enamel surface energy. The SLS decreased the protective potential of NaF on initial erosion, but no tested agent interfered with the protective effect of NaF on enamel erosive wear.