Aim: To determine the enamel solubility and depth of demineralization with laser bleaching and impact of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) when applied prior to and after laser bleaching. Materials and methods: The 40 specimens obtained from 10 human premolars were treated in accordance with manufacturer protocols; laser bleaching was performed using Opalescence Boost Gel (40% hydrogen peroxide) followed by laser activation using 36 mW/660 nm diode laser applied for 4 minutes at an energy fluence of 8.6 J/cm2. The study consisted of four experimental groups are as follows: • Group 1: Control (laser bleaching only) • Group 2: Pretreatment with CPP-ACP and laser bleaching • Group 3: Laser bleaching and post-treatment CPP-ACP • Group 4: Laser bleaching and post-treatment CPP-ACP and short burst of laser. Specimens were, thereafter, subjected to cariogenic challenge and further evaluated for enamel solubility by measuring the loss of Ca2+ ions and the depth of demineralization using polarized light microscopy. Results: Group 4 exhibited least enamel solubility and depth of demineralization (p < 0.0001) followed by groups 3, 2 and maximum by group 1. Conclusion: Post-laser bleaching application of CPP-ACP followed by a short burst of laser can provide exceptional resistance to enamel solubility (demineralization).