The Xinjiang region with residents from more than 13 minorities represents an area of many diverse ethnicities. This ethnic diversity in relation to their blood groups and immune status may have a consequential impact on the clinical status of married couples. To evaluate the risks of haemolytic disease in new-born infants, we investigated the rate of blood-group incompatibility among 487 married couples from four ethnic minorities, namely the Han, Hui, Uyghur and Kazak populations. Han minority married couples showed significantly different ABO, Rh and K phenotype frequencies between marrial relationship, whereas there was no significant difference in ABO, Rh and K phenotypes between the Uyghur, Hui and Kazak .There was a significant difference between ABO blood types in Han married couples, in the Kazak Rh-C phenotype and in the Uyghur Rh-D phenotype. The Hui married couples only demonstrated ABO, Rh and K phenotypes. The Hui minority showed the highest incompatibility rate for Rh-C and Rh-E phenotypes between mothers and their new-born infants. The highest incompatibility rate for the ABO phenotype occurred in the Kazak group. These results particularly demonstrate the clinical issues relating to ABO and Rh incompatibility, in the Kazak and Hui minorities, respectively.