OBJECTIVE: To evaluate the effectiveness of three different caries-preventing agents on artificial caries in a Streptococcus mutans-based caries model. METHODS: Sixty-five caries-free human molar enamel blocks were treated with a demineralization solution and a remineralization solution. The specimens were assigned to the following groups according to the caries-protective product applied: group A, chlorhexidine varnish; group B, fluoride-releasing chemically cured sealant; group C, fluoride-releasing lightcured sealant; group D, positive control (specimens that were subjected to de- and remineralization cycles without treatment with any caries-protective agents); and group E, negative control (specimens that were not subjected to de- and remineralization cycles). Samples in groups A–D were stored in demineralization solution with S. mutans and thereafter in artificial saliva. This procedure was performed for 30 days. Average fluorescence loss (ΔF) and surface size of the lesions were measured using quantitative light-induced fluorescence at baseline and on the 7th, 14th, and 30th days. RESULTS: After 30 days, group A demonstrated a significant increase in ΔF and the surface size of the lesions, no significant difference in comparison with the positive control group, and a significant difference in comparison with the negative control group. Group B showed no significant changes in both parameters at any of the measurement points. While group C showed increased ΔF after 14 days, no significant fluorescence change was observed after 30 days. CONCLUSIONS Both fluoride-releasing sealants (chemically or light-cured) show anti-cariogenic effects, but the use of chlorhexidine varnish for the purpose of caries protection needs to be reconsidered.