We quantified the influence of the elements of the extracorporeal oxygenation (ECMO) circuit on drug sequestration by focusing on the interactions between materials and drugs. Tubing of three different brands (Tygon/Maquet/Terumo) and oxygenators of two different brands (Maquet/Terumo) were used. Drugs included dexmedetomidine, meropenem, and heparin, which were dissolved in deionized water. Tubing was cut into approximately 7 cm sections and allowed drug solutions enclosed inside by clamping both ends. The oxygenator housing, gas membrane, and heat exchanger were dissected into approximately 1 g pieces and submerged into drug solutions. The experimental samples were then immersed in a water bath at 37°C for 1, 6, 12, and 24 h. After 24 h, the dexmedetomidine concentration was significantly reduced in all three types of tubing (<30.1%), the oxygenator heat exchanger from Maquet Inc. (41.8%), and the gas exchanger from Terumo Inc. (8.6%), while no significant losses were found for meropenem and heparin compared with the control group. The heparin concentration within the Maquet gas exchanger, on the contrary, increased significantly compared with the control group at 1 and 12 h (p < 0.05). Our in vitro study reveals that material selection is a vital part of ECMO development.