Bioline-coated polymethylpentene (PMP) membrane oxygenators (MO) are used for extracorporeal membrane oxygenation (ECMO) to improve gas exchange in patients with severe acute respiratory distress syndrome (ARDS). However, in some patients, long-term durability is limited due to fibrous and cellular accumulations on the gas exchange surface which can increase resistance to blood flow and diffusion path. These surface deposits of PMP MO after removal were studied with scanning electron and fluorescence microscopy techniques. Three of 31 patients supported by a PMP MO in an ECMO setting required a replacement of the oxygenator after a mean support interval of 11 ± 7 days due to an increase in flow resistance and an impairment of the gas exchange capacity. The membrane surface of the MO was covered with a fibrous network with imbedded platelets and red blood cells. A membranous structure composed of single cells and clusters of cells covered large areas of the PMP fibers. We assume that these cellular deposits lower the efficacy of ECMO. The identification of these cells could be a key for future therapeutic interventions and improvements in the development of MO.