Persistent unexplained hypoalbuminemia in end-stage renal disease is a marker of high morbidity and mortality. The aim of this work was to study the effect of changing the dialyzer membrane from a less biocompatible to a more biocompatible membrane and shifting back to the same less biocompatible membrane on serum albumin level. Our study included twenty-five patients with unexplained hypoalbuminemia (15 males and 10 females, age range 20-70 years) on hemodialysis at Kaser El-Eini dialysis unit, for 1-3 years duration. Predialysis serum urea, serum creatinine, serum albumin, CRP, and complete blood picture were measured monthly to all patients over 6 monthes which was our study duration. Also, spKt/V was calculated monthly to all patients during the study duration. From our study we reached the following results serum albumin level significantly increased on shifting patients from dialysis using the less biocompatible (cuprammonium) to the more biocompatible membrane (polysulfone). Then, serum albumin level significantly decreased after shifting back the patients from the more biocompatible membrane (polysulfone) to the less biocompatible (cuprammonium). Percentage positivity of CRP in our patients (taken as an index of biocompatibility reaction) significantly decreased when changing the dialyzer membrane from the less biocompatible (cuprammonium) to the more biocompatible membrane (polysulfone). CRP significantly rose back again when shifting back to the less biocompatible membrane (cuprammonium). Kt/V showed a significant increase when shifting from dialysis using the less biocompatible (cuprammonium) to the more biocompatible (polysulfone) membrane. Then, Kt/V showed a significant decrease after shifting back the patients from the more biocompatible (polysulfone) membrane to the less biocompatible (cuprammonium). We conclude from our study that membrane choice appears to have a direct effect on serum albumin level. This is probably by better biocompatibility reaction of the membrane and by more effeciency of dialysis.