Background: Infection with malaria under five remains a burden in sub Saharan African, and is associated with numerous preventable deaths. The clinical outcome of Plasmodium infection in endemic areas is influenced by erythrocyte polymorphisms including the ABO blood groups. This study reports the association of Malaria with the ABO blood group in children under 5years attending the outpatient‟s clinic at Bundibugyo hospital. Methods: This was a cross-sectional prospective study that carried out during the months of July to August, 2018, in Bundibugyo hospital. The study population comprised of children 7 months-5 years presenting with a febrile condition. Clinical and laboratory investigations were done using malaria rapid diagnostic tests and microscopy; Blood grouping was done by hemagglutination methods. Statistical analysis was done at bivariate and multivariate levels using SPSS Version 23.0 and P-values less than 0.05 were considered significant. Results: The prevalence of malaria was 14%. The most predominant blood group type were Rhesus (D) positive „O‟ at 54%; A‟ at 26.2%, B‟ at 18.6% and AB‟ at 1.3%;. Blood group A were 1.24 times more susceptible to have positive malaria test than those with blood group O (OR= 1.24, 95%C.I (1.01 – 2.48) ; P-value =0.003. B were 1.29 times more susceptible to have positive malaria test than those with blood group O blood (OR= 1.29, 95% C.I (0.88 – 3.23 ); P-Value = 0.011). The statistically outcome indicated that: blood groups A and B patients are more likely to have a positive malaria test compared to blood group O Conclusion and recommendations The prevalence of malaria is lower than the national average, Blood group O” Rh (D) positive was the most predominant; there is an association between ABO blood group and Malaria. The recommendation is that the current malaria control/prevention measures should be intensified and while managing malaria cases, client‟s blood groups should be determined to help in management of vulnerable groups.

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