To investigate the involvement of systemic oxidative stress in the pathogenesis of murine cerebral malaria, mice were infected with the Plasmodium berghei (P. berghei) ANKA 6653 strain. Serum tryptophan (Trp), kynurenine and urinary biopterin, liver, brain, spleen and serum superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and nitrite and nitrate (NOx) levels were measured on day 7 post-inoculation. Our data showed a significant decrease in SOD and an increase in GPx activity and MDA level in all the examined biological materials (p < 0.05), except spleen. Conversely, GPx activities in spleen were depleted, while SOD and MDA levels remained unchanged. Increased MDA levels might indicate increased peroxynitrite production, lipid peroxidation and oxidative stress. Also, elevated urinary biopterin, which was accompanied by increased NOx (p < 0.05), may support the inhibition of Trp degradation (p > 0.05). The excessive NO synthesis in P. berghei infection may be related to the up-regulation of inducible NO synthase, which was in accordance with the increased biopterin excretion. Thus, the large quantities of released toxic redox active radicals attack cell membranes and induce lipid peroxidation. Although P. berghei infection did not demonstrate systemic Trp degradation and related indoleamine-2,3-dioxygenase activity, it may cause multi-organ failure and death, owing to host-derived severe oxidative stress.