To investigate membrane lipid abnormalities and their possible role in copper deficiency anemia, we studied lipids, osmotic fragility, and viscosity of red blood cells (RBCs) of rats fed diets containing 1.1 mg Cu/kg (deficient, Cu-) and 6.0 mg Cu/kg (supplemented, Cu+) at age 3 wk for 9 wk. Data show an increase in cholesterol of 43% and in phospholipids of 38% per cell in Cu- compared with Cu+ rats. Thin-layer chromatography of RBC lipids showed an increased amount of phospholipid-malonyldialdehyde adduct in Cu- (0.70 +/- 0.35% [means +/- SD] of total phospholipids) compared with Cu+ (0.29 +/- 0.19%) rats, suggesting increased membrane lipid peroxidation in Cu- RBC. Osmotic fragility of RBCs from Cu- rats was lower. RBC viscosity was significantly higher in Cu- than in Cu+ rats at shear rates of 23, 11.5, and 5.75 shear/s and was similar at shear rates 115 and 46 shear/s. Increased cell viscosity caused by lipid loading and crosslinking of membrane components caused by lipid peroxidation may have a role in the reduced RBC survival and anemia in Cu deficiency.