Correlation between ABO/Rhesus blood group, Sickle cell disease (SCD) and Diabetes mellitus (DM) was investigated in Okwe, Asaba, Delta State and Ihiala, Anambra State,Nigeria. 100 proven cases of sickle cell patients (HBSS) from the sickle cell clinic in the General Hospital, Okwe, Asaba, Delta State, Nigeria, were studied. 200 normal individuals, 100 with genotype AA and 100 with genotype AS were taken as control for comparison from Okwe town. Furthermore, 50 proven cases of adults diabetic mellitus type2 from the diabetic clinic of our Lady’s of Lourdes Hospital Ihiala, Anambra State were studied. Samples of 50 normal adult individuals were taken from the Hospital town as control for comparison. In the ABO/Rhesus blood group and SCD, the result showed that there was a correlation between ABO/Rhesus blood group and sickle cell disease (p<0.05). It was also observed that blood group O has the highest frequency distribution among the sicklers (63%), followed by blood group B (20%), then blood group A (17%), the least was AB blood group with O% distribution. For Rhesus blood system, the prevalence of Rh positive and Rh negative was studied against the hemoglobin genotypes. Rh positive was 96%for SS, 74% for AA, and 92% for AS. Rh negative was 4% for SS, 26%for AA and 8% for AS. This showed that Rh positive has the highest prevalence in SS while Rh negative has the lowest prevalence in SS,[P ABO\Rhesus blood group and DM, there was no correlation between ABO/Rhesus blood group and adult type 2 diabetes mellitus (P>0.05). It was also observed that blood group O (78%) was most commonly distributed in diabetes mellitus type2, followed by A (22%), blood group 0 (0%) and AB (0%) did not show any incidence of type2 diabetes mellitus. When Rh positive and Rh negative where matched against DM and the control, Rh positive was 94% in DM and 88% in control (P>0.05). Rh negative was 6% in DM and 12% in control, (P>0.05). It was observed that Rh positive was more in DM than the control, and Rh negative was more in control than in DM patient. Therefore, correlation between ABO/Rhesus blood group and diabetes mellitus type 2 was not proven. It is accordingly, concluded that ABO/Rhesus blood group has positive correlation with sickle cell disease and fell short of such correlation with diabetes mellitus.