Treatment of malaria in Africa is becoming increasingly difficult due to increasing resistance to antimalarial drugs. The invivo antiplasmodial activity of 70% ethanol extract of Citrus sinensis and its n-hexane, ethyl acetate, and aqueous fractions was investigated in this study. Healthy Albino mice were inoculated with Plasmodium berghei and a hydro alcoholic crude extract of C. sinensis and its solvent fractions were administered at doses of 300, 500 and 700 mg/kg. The antipyretic effect of the extract was determined in rats using Brewer’s yeast- induced pyrexia. The phytochemical analysis and the acute toxicity of the crude extract were also evaluated. The crude extract and fractions showed varying degrees of antiplasmodial activity. The percentage suppression of parasitaemia was 33.65, 43.93 and 53.27% at 300, 500 and 700 mg/kg respectively. The ethyl acetate fraction was the most potent among the fractions exhibiting percentage chemo-suppression of 16.48, 19.81 and 26.42%, at 300, 500 and 700mg/kg respectively. There was no significant reduction in the rectal temperature at the doses tested (P>0.05). Acute toxicity test of the crude extract indicated an LD50 more than 5000 mg/kg. The qualitative phytochemical analysis revealed the presence of tannins, saponins, flavonoids, alkaloids, proteins and carbohydrates. These results indicate the potentials of the stem of Citrus sinensis in combating malaria.