Malaria is a blood disease caused by the bite of Anopheles mosquito. It is also a major healthrnproblem in developing countries accounting for 2-3 million deaths per year. The burden ofrnmalaria is increasing especially in sub-Saharan Africa because of drug and insecticidernresistance, social and environmental changes, creating a major challenge in providingrnpatients with this infection with effective malaria chemotherapy. Severe malaria affectsrnalmost all blood components and is a true hematological infectious disease. Anemia andrnthrombocytopenia are the most frequent malaria-associated hematological complications andrnthey play a major role in malaria pathogenesis. Hypoglycemia is a frequently encounteredrncomplication in severe Plasmodium falciparum malaria, which is usually ascribed torndecreased glucose use and impaired glucose production caused by the inhibition ofrngluconeogenesis. The Gambella People's Regional State is located at South West of Ethiopiarnand malaria is the leading cause of morbidity and mortality in this region. The objective ofrnthis study was to investigate the effect of severe Plasmodium falciparum malaria on somernbiochemical and hematological parameters in Gambella region at Gambella General Hospitalrnon adult males aged from 18-55. Hyperparasitemia in the adult males was considered as anrnimportant criterion for selection of individuals with severe malaria. Fasting blood glucosernand hematological parameter (RBC, Hb, Hct, MCV, MCH, MCHC and PLT) were measuredrnin patients (n = 60) and control subjects (n = 40). The results were analyzed using student t-rntest and indicated significant difference in the hematological parameters between the malariarninfected and non-infected subjects (p < 0.01). Adult males with severe malaria hadrnsignificantly decreased levels of RBC, Hb, Hct and PLT also a significantly decreased levelrnof fasting blood glucose (p < 0.01) but the level of MCV, MCH and MCHC were notrnsignificantly decreased when compared with the control group (p > 0.05). Hb and fastingrnblood glucose are positively correlated with demographic indicators and PLT negativelyrncorrelated with the demographic indicators in the study groups and control groups. The studyrnconcluded that investigation of biochemical parameters and hematological parametersrnshowed certain changes of a sub-clinical pattern and severe Plasmodium falciparum canrncause significant hematological changes with high incidence of thrombocytopenia andrnanemia. Consideration of these changes in adult males with severe Plasmodium falciparumrnmalaria might effectively reduce morbidity and mortality.rnKey words: - Fasting blood glucose, severe malaria, Plasmodium falciparum parasites,rnHematological parameters, Gambella, Ethiopia