The aim of this study was to evaluate, in vivo, the immediate masking effect of white spot lesions (WSLs) treated with an infiltrant resin (IR). The investigation was conducted on 40 young adolescent and adult patients (11 to 23 years old) who presented with at least one permanent maxillary or mandibular anterior tooth with active WSLs on the enamel (ICDAS score 2). Before resin infiltration, the color of both the WSLs and the sound adjacent enamel (SAE) was evaluated by a digital spectrophotometer (CIELab). Subsequently, a resin infiltration technique (Icon) was performed on the WSLs according to the manufacturer's instruction. At the end of the clinical session, the color of the IR was evaluated. The color difference (ΔE) was calculated between WSL × SAE, WSL × IR, and IR × SAE, and then analyzed using one-way analysis of variance (ANOVA), followed by the Tukey's test. The L*, a*, and b* values of WSL, SAE, and IR were compared using the Student's t test for related samples (α = 5%). The ΔE observed was 5.93 ± 0.41 on the WSL × IR comparison, and 5.77 ± 0.41 on the IR × S AE one, indicating that the color of the WSL changed after treatment, but that the infiltration did not fully camouflage the WSLs when compared with the SAE. The lightness was higher for the SAE than for the IR. It was concluded that the IR treatment was not able to camouflage the color of the WSLs when compared with the SAE. However, the treatment was able to attenuate the discoloration of the demineralized dental enamel.