Multidirectional tests were carried out to study the influence of the type and temperature of serum lubricant on the wear and friction of vitamin E stabilized, extensively crosslinked ultrahigh molecular weight polyethylene (VEXLPE) against polished CoCr. To minimize the rates of protein denaturation and microbial growth, cold wear tests were performed for the first time so that the serum lubricant was at a refrigerator temperature of 4 °C. The highest wear factors and coefficients of friction were observed at the refrigerator temperature and the lowest at body temperature where the rates of protein denaturation and microbial growth were expected to be at their maximum. The VEXLPE mean wear factor in alpha calf serum (ACS) decreased by two orders of magnitude as the lubricant bulk temperature increased from 4 °C to 37 °C. Thermal analysis indicated that the contact temperature in the pin-on-disk test was less than 2 °C above the lubricant bulk temperature. It appears that a wide range of polyethylene wear rates and coefficients of friction can be obtained depending on the temperature. The type of serum also strongly affected the obtained wear rate at and above 20 °C.