Purpose: . This study aims to evaluate the combined effect of reduced thickness in different regions on the fracture resistance of monolithic zirconia crowns. Materials and methods: . Seven nickel-chromium dies were generated from a 3D model of mandibular first molar using the digital scanner with the following geometries:1.5 mm occlusal reduction, 1.0 mm deep chamfer. Based on the abutment model, Zirconia blocks (Luxen Zirconia) were selected to fabricate Sixty-three zirconia crowns with occlusal thicknesses of 0.3 mm, 0.5 mm, and 1.5 mm, and different axial thicknesses of 0.3 mm, 0.5 mm, and 1.0 mm. All crowns were cemented by resin cement. Next, the crowns were subjected to load-to-fracture test until fracture using an electronic universal testing machine. In addition, fracture patterns were observed with a scanning electron microscope (SEM). Two-way ANOVA and the Tuckey HSD test for post hoc analysis were used for statistical analysis (P < .05). Results: . The mean values of fracture resistancerecorded was higher than the average biting force in the posterior region. The two-way ANOVA showed that the occlusal and axial thickness affected the fracture resistance significantly (P < .05). However, the effect of axial thickness on fracture resistance did not show a statistical difference when thicker than 0.5 mm. The observed failure modes were partial or complete fracture depending on the severity of crack propagation. Conclusion . Within the limitations of the present study, the CAD-CAM monolithic zirconia crown with extremely reduced thickness showed adequate fracture resistance to withstand occlusal load in molar regions. In addition, both occlusal and axial thickness affected the fracture resistance of the zirconia crown and showed different results as combined.