In recent years, the use of spacer fabrics as cushioning materials in protective clothing and equipment has been highlighted. Thanks to the three-dimensional structure of spacer fabrics, they demonstrate special features. In addition to comfort requirements, the spacer fabrics exhibit good compressive characteristics and energy absorption, which are essential for human body protection against impacts. The cushioning performance of spacer fabric is highly dependent on the compression characteristics of the fabric. Consequently, investigating the relationships between fabric structure and the compression property of spacer fabrics is essential. The goal of this research is to consider the effect of fabric structure on the compression behavior of weft-knitted spacer fabrics made for protective applications. To this end, weft-knitted spacer fabrics with various knit patterns in the surface layer have been fabricated. The results demonstrate that the fabric's compression resistance increases by increasing the number of miss stitches in successive courses in the surface layer. Furthermore, increasing the number of miss stitches in successive courses in the surface layer decreases the fabric's resilience, thickness change, and relative compressibility while increases the absorbed energy and dissipated compression energy of the fabric. Eventually, since spacer fabrics consist of the knit stitches on their surface layers absorb higher energy and demonstrate better resiliency and relative compressibility compared to spacer fabrics consist of the miss and knit stitches on their surface layers, these structures are more appropriate for cushioning applications.