Objective: This study aimed to evaluate the color change of CAD/CAM resin matrix ceramic, which was exposed to three different whitening mouth rinses and artificial saliva for 12 and 180 hours. Material and Methods: A total of 60 samples were produced from prefabricated CAD/CAM resin matrix ceramic blocks for experimental study. The samples were randomly divided into four subgroups according to the whitening mouthrinses: Listerine Advanced White, Colgate Optic White, Oral B 3D White Luxe, and artificial saliva. Spectrophotometric measurements were made from each sample at 3 different times, before (initial) exposure to mouthrinses, 12 hours and 180 hours after exposure (∆E001, ∆E002 and ∆E003). While using the generalized linear models method for the comparison of ∆E00, ∆L, ∆a, and ∆b color changes according to the mouthrinse and exposure time; multiple comparisons were made with the Tukey HSD Test. The significance level was taken as p<0.050. Results: The results of the two-way analysis of variance showed that the used mouthrinse and the exposure time had a statistically significant effect on the ∆E00 values representing the color change (p<0.001), while the interaction between the mouthrinse and the time of use did not play an important role (p=0.165). Conclusion: After exposure time of 180 hours, all whitening mouthrinses induce color change of resin matrix ceramics above clinically noticeable level.