Abstract Hyperbilirubinemia often accompanies liver failure; therefore, artificial liver support devices are currently used as a bridge to more definitive treatments to eliminate water-soluble and albumin-bound toxins. We report 2 patients, of which, after liver transplantation, the first experienced early allograft dysfunction and the other hyperbilirubinemia linked to chronic rejection. After 3 cycles of coupled plasma filtration adsorption (CPFA), the bilirubin promptly decreased in both cases. CPFA is an extracorporeal therapy that uses plasma filtration associated with an adsorbent cartridge and hemofiltration to remove cytokines and inflammatory mediators associated with septic shock, severe sepsis, and multiple organ dysfunction syndrome. Each cycle of treatment lowered the bilirubin of our patients by ∼40%. CPFA deserves attention as a potential inexpensive short-lasting device to treat hyperbilirubinemia after liver surgery or transplantation. Moreover, the effects of CPFA should be further studied to address inflammatory mediators in chronic rejection after liver transplantation or other immunologic disorders.