Objectives The aim of this study was to evaluate the effects of in-office and at-home bleaching agent applications on the surface topography and microhardness of artificially demineralized enamel. Materials and Methods A total of 224 enamel specimens were prepared using bovine sound central incisors. 4 mm × 4 mm enamel windows were exposed on the buccal surfaces covering the remaining surface with nail varnish. Samples were immersed in a demineralizing solution for 16 hours to produce artificial caries lesions, then divided into four groups according to the bleaching agent’s type and concentration. Group I; in-office bleaching 35% hydrogen peroxide (HP) (Whiteness HP Maxx; FGM, Brazil), Group II and Group III at-home bleaching 16 and 22% carbamide peroxide CP, respectively (Whiteness Perfect). Group IV; control (not bleached). The microhardness Vickers hardness number (VHN) was measured at the baseline, after demineralization, and after bleaching consequently. The micro-surface changes of the enamel surface after demineralization and bleaching were evaluated by scanning electron microscope (SEM). Statistical Analysis Data were evaluated by the one-way analysis of variance (ANOVA) test followed by Post Hoc Tukey’s and Fisher’s least significant difference. Tow- sided p -values were considered statistically significant at p ≤ 0.05. Results A significant reduction was noticed in the enamel microhardness after demineralization p < 0.05. However, there is no statistically significant difference between the mean VHN of the demineralized and bleached enamel ( p > 0.001). SEM images showed significant changes on the surface of the demineralized enamel after bleaching (pattern type III). Conclusions The low and high concentrations of HP and CP bleaching agents increased the demineralization severity of artificial caries lesions without significantly altering their microhardness values.