Hepatitis C virus (HCV) has a major impact on public health. In spite of the progress made in the prevention of transfusion-transmitted infections over the last years, these still occur, especially in multi-transfused patients such as sickle cell anemia patients. Sickle cell disease (SCD) is highly prevalent in Eastern Saudi Arabia. Little is known about the prevalence of HCV in Saudi sickle cell disease patients. The present study aimed to assess HCV and HBV antigens, antibodies and viral genome among sickle cell anemia patients in a tertiary hospital in Eastern Saudi Arabia. Methods used included measurement of HCV antigen and antibodies using the novel HCV antigen/antibody combination assay, assessment of HCV core antigen and measurement of viral genome using standard commercial kits. Of the 138 sickle cell disease samples tested, 5 (3.6%) samples gave positive results. Their hemoglobin ranged between 7.8 and 10.1 g/dL, their erythrocyte count ranged between 3.1￥106 and 3.9￥106. Out of these 5 samples, 4 were also positive by the HCV Core Ag assay and by the HCV RNA PCR test (80%). None of the control group was positive. Seven patients were positive for HBs antibodies. One sample was positive for HBsAg, and this indicates chronic carrier state. Improving the testing for blood-borne infections such as HCV and HBV will result in better control of these infections in sickle cell disease patients which will inevitably lead to lower mortality and morbidity in this group of patients.