This paper presents a comparative study on the mechanical properties of seven monofilaments of 0.12 mm diameter made with different polymeric materials including PET, PBT, PE, PP, and PA6 in order to assess their suitability for being spacer yarns for developing high-quality spacer fabrics. Their support capability and elasticity corresponding to fabric compression resistance and resilience, respectively, were evaluated by analyzing the tensile stress–strain relationships and residual strains of monofilaments subjected to cyclic tensile loading. Slack and taut heat setting on the monofilaments were also considered to select a proper heat setting method for their spacer fabrics. The mechanical properties of the monofilaments were explained by using the supramolecular structure information from X-ray diffraction and sonic orientation tests. The results showed that PET monofilaments have much higher moduli than the other monofilaments and possess better support capability as spacer yarns for spacer fabrics. PET monofilaments also have better elasticity under small deformation below 5% strain than the other monofilaments, but their elasticity is inferior under large deformation above 5% strain. PET monofilaments are suitable for being spacer yarns to achieve high compression resistance and resilience for spacer fabrics. The PET monofilament with higher molecular weight possessed the lower Young’s modulus which is good for the knitting process. PET monofilaments with high molecular weight and taut heat setting are recommended for producing spacer fabrics with high compression resistance and resilience, especially for small fabric deformation.