The effect of antioxidant (Vitamin E) on the efficacy of Artesunate was investigated using Plasmodium berghei infected mice. Fifty (50) adult albino mice weighing between 15-25g were used for this study. There were five groups of ten animals each per group. Group I was the normal control group without the parasite and untreated, group II was infected with malaria parasite and 0.9% normal saline was administered, group III was infected with the parasite and treated with artesunate, group IV was infected with the parasaite and vitamin E was administered and group V was infected with the parasite and combination of artesunate and vitamin E were administered. Parasitaemia level and haematocrit (PCV) were monitored upon the administration of antimalaria drug -artesunate, vitamin E, normal saline and combination therapy of both vitamin E and artesunate. The life span of the infected mice was found to be between the 7 and the 10 day post inoculation, while the LD of the parasite was 156626.2 parasite/μl of blood. Artesunate was observed to rapidly clear the parasite with parasitaemia level of 21632.4 ± 513.3 parasite/μl on the 6 day, 11209.9 ± 363.7 parasite/μl on the 7 day, 1359.7 ± 14.3 parasite/μl on the 8 day, 7.8 ± 2.4 parasite/μl on the 9 day and zero parasitaemia on the 10 day. The effect of artesunate was significantly reduced when co-administered with vitamin E (p < 0.05) with parasitaemia 30542 ± 362.5 parasite/μl on the 6 day, 24705.2 ± 489.9 parasite/μl on the 7 day, 15485.0 ± 563.2 parasite/μl on the 8 day, 947.6± 37.8 parasite/μl on the 9 day and 8.0 ± 2.7 parasite/μl on the 10 day. The study suggests that co-administration of vitamin E with artesunate could reduce the efficacy of artesunate in malaria infection.