Objective: Since little is known about the effects of carbamide peroxide (CP) containing fluoride (F) or calcium (Ca), this study evaluated the effects of experimental and commercially available bleaching agents, with or without F and Ca, on enamel. Method and Materials: Sound enamel slabs were randomly divided into six groups (n = 10): placebo gel (PLA); Whiteness (WHI-10% CP; FGM); Opalescence F (OPA-10% CP+F; Ultradent); Pola Night F (PN-10% CP+F; SDI); and experimental gels: 10% CP + F (CPF) and 10% CP + Ca (CPCa). The samples were submitted to 6-hour gel applications daily for 14 days and stored in remineralizing solution after treatment. Enamel microhardness measurements were performed at baseline and after bleaching. In addition, the analytical concentrations of F and Ca and the pH of the water used to rinse the bleached surface were analyzed by means of ion-selective electrode, atomic absorption spectroscopy, and pH meter, respectively. Results: Enamel surface microhardness significantly decreased after bleaching with nonenhanced 10% CP (WHI). The chemical analyses suggest F uptake promoted by high-concentrate F bleaching gels (CPF, OPA, and PN) and a F loss with nonenhanced 10% CP bleaching gels (PLA, WHI). CP agent enhanced with Ca (CPCa) also caused Ca enamel uptake. Conclusion: Enamel was susceptible to mineral changes during bleaching treatment, but mineral loss was minimized by the addition of F and Ca to bleaching agents.