To evaluate the influence of air-abrasion of enamel with three different desensitizing powders on the whitening effect of a bleaching gel containing 40% H2O2, which was used for in-office tooth bleaching. Forty human incisors, extracted and prepared, were acquired for this study and subsequently randomized into four groups (n = 10). The control group specimens underwent no pretreatment prior to the bleaching procedure, whereas the remaining three groups underwent air abrasion using distinct desensitizing powders; (a) Sylc, which contains bioglass 45S5; (b) BioMinF, which contains calcium phospho-fluoro-silicate glass; and (c) MI Pearls, which contains nano-hydroxyapatite, 1 h preceding the Opalescence Boost PF 40% bleaching procedure. Color measurements were conducted using a double-beam UV-Vis spectrophotometer at four distinct time points (prior to bleaching, 24 h, 15 days, and 30 days post-bleaching). Tooth color change outcomes revealed that there were no statistically significant results with respect to the interaction of the two criteria (treatments and time) (p = 0.990). Additionally, there were no statistically significant results with respect to the main effects of treatments (p = 0.385), while there were statistically significant effects with respect to the time criterion (p = 0.013). The use of the tested desensitizing powders prior the bleaching procedure did not affect the tooth color change induced by the tested bleaching agent. Tooth color change and whiteness are not affected by air-abrasion desensitizing treatments when applied prior to in-office bleaching procedures.