Cell-free (cf) DNA in maternal circulation is increasingly investigated in pregnancy. This study aimed to determine whether sickle-cell trait women had quantitative differences of cf-DNA to controls and if there was an ethnic difference between the cf-DNA levels of Northern European and African/African-Caribbean populations. Non-invasive prenatal diagnosis, through quantification of fetal and total cf-DNA, was tested in 33 pregnant women at risk of carrying a fetus affected with sickle-cell disease and 124 control pregnancies. A significant variation in cf-DNA was found between ethnic groups, which should be taken into consideration in future studies measuring cf-DNA.