BACKGROUND Parenteral nutrition (PN) is a hyperosmolar solution composed of glucose, amino acids and a lipid emulsion, which is often used despite well-known side effects and complications. OBJECTIVES In this study the hypothesis was tested that PN could affect hemorheology. METHODS The influence of increasing plasma concentrations (0, 4, 10 and 25%) of the 3-in-1-mixture of PN on various rheological parameters were studied in vitro. The influence of the individual components was studied with plasma concentrations of 10, 10 and 5%, respectively. Hematological and coagulation tests were performed. Blood viscosity and red blood cell (RBC) aggregation were measured and platelet aggregation in flowing blood was assessed with a PFA-100 instrument. RESULTS It was found that PN induced RBC shrinkage, which was partially reversible. It reduced RBC aggregation measured by low shear viscosity or RBC sedimentation. Platelet aggregation was strongly inhibited. Coagulation tests were not affected. Investigations with the single components of PN showed that the RBC shrinkage was mainly caused by the amino acid solution and the inhibition of platelet aggregation by all 3 components. The lipid emulsion in higher plasma concentrations led to echinocytosis, indicating that the lipids interact with the outer half of the membrane lipid bilayer. CONCLUSIONS High concentrations of PN affect blood rheology in several ways. The strongest effect was an inhibition of platelet aggregation, which may have a clinical relevance. Other effects such as RBC shrinkage and decreased RBC aggregation occurred only at high PN concentrations, which are reached in vivo at the infusion site.