Backgrounds: Malaria is a major public health problem in the tropical and subtropical areas of the world, including Africa. Most cases of malaria in Africa are caused by Plasmodium falciparum. Objectives: This study was aimed to assess the hematological changes in patient with falciparum malaria and to estimate the incidence of leucopenia, thrombocytopenia, and its response to anti-malaria therapy, and to correlate the association of the hematological changes with P. falciparum-positive (study group) and P. falciparumnegative (control group). Methodology: A total of 453 participants (353 cases and 100 as control group) were
enrolled in this study, all of them were randomly selected from Elnihoud Teaching Hospital, Elnihoud Locality, West Kordufan State, Sudan. Questionnaire was filled by every participant and thick and thin blood films for malaria were prepared and stained by giemsa stain and the CBC was done by sysmex automated hematological analyzer. Results: Thrombocytopenia, leucopenia, microcytic hypochromic red blood cells and relative lymphocytosis have significant association with falciparum malaria with Pvalues 0.008, 0.001, 0.008, and 0.004, respectively. Conclusion: Patients with thrombocytopenia and/or leucopenia with malaria should
receive anti-malaria therapy and follow-up by CBC, and shouldn’t be hurried for a bone marrow examination.