Cross-laminated timber (CLT) panels are favored for their lightweight nature and widespread applications in construction. However, there are concerns that the production of these panels may involve excessive raw material usage relative to the structural requirements in specific scenarios. This paper investigates the structural implications of incorporating air gaps within the cross layers of CLT panels, with a focus on their potential to enhance material efficiency without compromising load-bearing capacity. Various configurations, including solid panels and panels with centrally and shifted arrangements of voids in different sizes, were examined. Employing experimental testing and numerical analysis, the study explores variations in rolling shear strength, bending stiffness, and deflection across CLT panel configurations. Shear tests on a small scale and four-point bending tests at a full scale were conducted on CLT panel samples. The findings reveal that the presence of air gaps significantly impacts the structural properties of CLT panels. Among the different configurations tested with air gaps between lamellas in cross layers, those with lamellas, whose center is shifted relative to each other with the highest overlap across different cross layers exhibited greater rolling shear strength. This underscores the importance of the strategic placement of air gaps in refining CLT panel design for both efficiency and performance. Additionally, the study introduces adjusted smeared shear modulus values for the CLT panels with air-gaped configurations, which are correlated with solid panel properties. In four-point bending tests, it was observed that panels with wider air gaps showed increased deflection and decreased stiffness compared to solid panels without air gaps. The study suggests that the stiffness of CLT panels with air gaps can be effectively predicted using the modified gamma method when incorporating the adjusted rolling shear modulus into calculations. Furthermore, the Timoshenko method requires adjusting the shear correction factor, κ_s, to predict beam deflection effectively.