Objective: The aim of this laboratory study was to investigate the effect of three commercial bleaching agents and Tooth MousseTM containing 10% w/w casein phosphopeptide–amorphous calcium phosphate on the hardness of tooth enamel. Methods: Sixteen human enamel specimens were exposed to one of three commercial bleaching agents with or without subsequent exposure to Tooth MousseTM. Nanoindentation was used to measure the hardness and reduced modulus before and after treatments. Results: When bleaching materials were applied for a short period of time following the manufacturers’ instructions, there was an increase in enamel hardness and reduced modulus for some bleaching groups, with no statistically significant difference from the baseline values. After extended bleaching periods a statistically significant decrease in enamel hardness and reduced modulus was found and after applying Tooth MousseTM post-bleaching, the hardness and reduced modulus returned to close to baseline values. Conclusion: The application of bleaching agents for an extended period of time significantly decreases enamel hardness and the reduced modulus. The application of Tooth MousseTM after bleaching was able to reestablish the baseline enamel hardness and reduced modulus, decreasing the adverse effects of bleaching enamel.