PURPOSE: To evaluate the effect of different surface treatments on luting CAD/CAM composite resin workpieces. MATERIALS AND METHODS: One-hundred eight (108) composite CAD/CAM block sections (Lava Ultimate) 3 mm in thickness were polished up to 4000 grit and then randomly assigned to 6 experimental groups according to the applied surface treatment (no treatment, sodium bicarbonate [NaHCO3], glycine, alumina [Al2O3], CoJet, and SilJet). After standardized sandblasting procedures, 2 block sections from each group were randomly chosen for the qualitative SEM evaluation of the sandblasted surfaces. The remaining 96 CAD/CAM block sections were luted in pairs using a bonding agent (Single Bond) and a restorative composite resin (Filtek Ultimate). Specimens were aged for 2 weeks in 37°C water with 3000 thermal cycles (5°C/55°C), the microtensile test was performed (n = 30), and the values were statistically analyzed with ANOVA and Tukey's HSD post-hoc test (p = 0.05). RESULTS: The qualitative SEM evaluation of the sandblasted surfaces showed that sodium bicarbonate and glycine had almost no conditioning effect on the CAD/CAM composite resin. In contrast, aluminum oxide, CoJet, and SilJet had a profound conditioning effect on the CAD/CAM composite resin. No treatment, sodium bicarbonate, and glycine specimens were debonded after thermal stressing (0 MPa), while aluminum oxide, CoJet, and SilJet showed high microtensile values (Al2O3: 104.45 ± 18.76 MPa; CoJet: 105.55 ± 11.88 MPa; SilJet: 105.02 ± 20.84 MPa), which were not statistically significantly different from each other. CONCLUSION: Aluminum oxide-based sandblasting powders are the best choice for the surface treatment of CAD/ CAM workpieces.