Background: Protein-calorie malnutrition is present in 30–50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to incompatibility of the dialyzer during the dialysis session. Methods: Five patients were dialyzed during 2 periods of 3 weeks (cross-over) with either a single-use low-flux polysulfone or cellulose triacetate (biocompatible) or a single-use cuprophan (bio-incompatible) membrane. As a measure of whole body protein metabolism, a primed constant infusion of L-[1-<sup>13</sup>C]-valine was used during a 4-hour dialysis session. Results: Cuprophan was a more powerful activator of the complement system than other membranes. Protein metabolism parameters during both study protocols were not different and resulted in the same protein balance during polysulfone/cellulose triacetate (–15 ± 3) and cuprophan (–13 ± 2 µmol/kg/h) dialysis. Conclusion: In stable hemodialysis patients with no apparent complications, protein metabolism during dialysis is not affected by the compatibility of the dialysis membrane.