The decrease in tensile strength and increase in specimen weight due to lipid diffusion in a biocompatible thermoplastic elastomer was studied and quantified. Mechanical and viscoelastic properties of poly(styrene-isobutylene-styrene) (SIBS) block copolymer are critical to determine feasibility of certain load bearing in vivo applications. Moreover, changes of these properties due to the presence of lipids must be well understood for long-term bio implantation. Dumbbell specimens were thermoformed via injection molding and weights were recorded. Lipid uptake in the body was simulated by specimen immersion in palm and castor oils at 25 °C and 37 °C. After only 96 hours of immersion at body temperature (37 °C), dumbbell weight increased by 6% and 0.3% for palm oil and castor oil, respectively. These values correspond to a reduction in ultimate tensile strength of approximately 30% and 10%, respectively. These results restrict the use of this biocompatible polymer in certain critical components due to the high concentration of lipids in vivo. Based on these significant and rapid reductions in tensile strength in the presence of lipids, it is of vital importance to fully understand the bio-durability and lipid uptake characteristics of SIBS for future design and performance prediction of implantable devices. Further, the results highlight the necessity of improving lipid resistance in order to fully exploit the biocompatibility of SIBS.