The metabolism of lipids may be altered in sickle cell anemia and beta-thalassemia patients. Plasma lipids in 24 patients with sickle cell anemia (SS), 15 patients with sickle/beta-thalassemia (ST), 19 individuals with sickle cell trait (AS) and 62 healthy individuals (AA) were measured. Total cholesterol concentrations in both sexes with sickle cell anemia (SS males: 104.7, SS females: 142.7 mg/dl) and sickle/beta-thalassemia (ST males: 116.7, ST females: 137.5 mg/dl) were lower (P<0.05) than AS (AS males: 171.5, AS females: 185.4 mg/dl) and normal individuals (AA males: 173.7, AA females: 183.0 mg/dl). The mean HDL-cholesterol in males with SS (35.6 mg/dl) and ST (40.7 mg/dl) were (P=0.001) lower than AS males (58.9 mg/dl). However, the mean HDL-cholesterol in females with SS (43.2 mg/dl) was lower (P<0.001) than AS females (62.7 mg/dl). The mean LDL-cholesterol of males with SS (53.8 mg/dl) was lower (P<0.01) than AS (89.4 mg/dl) and control males (115.9 mg/dl). Males with ST had a lower (P<0.001) LDL-cholesterol (58.0 mg/dl) compared to control males. In females with SS the LDL-cholesterol (78.3 mg/dl) was lower (P<0.001) than control females (124.3 mg/dl). However, females with ST had lower (P<0.05) LDL-cholesterol (61.6 mg/dl) than AS (101.7 mg/dl) and control females. There was no significant difference in total concentrations of cholesterol and triglycerides between males and females with AS and those with normal hemoglobin. However, the HDL-cholesterol in both genders with AS was higher (P<0.001) than normal subjects. Also, the concentration of LDL-cholesterol in both males and females with AS was lower than control males (P<0.05) and females. Hemolytic stress could be associated with a significant reduction in plasma lipids and lipoproteins. It appears that patients with sickle cell anemia and individuals with sickle cell trait are at a lower risk for coronary artery disease.