The knee is the most used joint in the human body and is also most prone to injuries. Knee braces are medical devices used in the treatment of some form of injuries providing compression and warmth to the joint thus promoting healing. They can also be used for protection in several contact sports. At the moment there are no regulations governing the textile materials used in braces. The authors believe that knitted spacer fabrics have the desirable mechanical and comfort properties which could make these materials suitable for some medical applications. Commercially available knee braces have been tested and analyzed for their mechanical as well as thermophysiological properties. A range of novel spacer fabrics have been designed, developed, and characterized for comparison with commercial products. It has been found that knitted spacers can be engineered in terms of yarn type and structure used in each of the three layers in order to match and even outperform the properties exhibited by commercially available products, such as neoprene and other knitted fabrics, including composite materials. The test results obtained for a range of existing and novel products studied in this work have been explained in terms of their raw material, structure, and finishing treatments applied to them.