This study aims to investigate the effect of surface material type, monofilament yarn diameter and inclination angle on the thermal comfort and moisture management properties of the flat knitted spacer fabrics. For this purpose, seven different spacer fabrics were knitted by using different type of surface materials (Multifilament polyester and Coolmax((R))) and by varying the monofilament yarn parameters (yarn diameter of 0.28, 0.38, 0.48 mm and connecting distances of spacer yarns (three, five, seven needles shifting). The thermo-physiological comfort (air permeability, water vapour permeability and thermal resistance) and liquid moisture transport capabilities of these fabrics were tested and evaluated statistically. The results indicated that, the most effective factor on the thermophysiological comfort and moisture management properties is the raw material. Due to their channelled structure, fabrics containing Coolmax((R)) yarns with higher air permeability, water vapour permeability index, thermal resistance and OMMC values provide better thermo-physiological comfort and liquid moisture transfer properties.