Superoxide dismutases (SOD’s) are key enzymes which catalyze the dismutation of the O2- free radical to hydrogen peroxide and oxygen. Hence SOD is an important enzymatic, antioxidant defense in all cells exposed to oxygen. Two different SODs have been described in mammalian cells: cytosolic, Cu-Zn containing enzyme, and, mitochondrial Mn- dependant enzyme. A third Fe- containing SOD is known to occur in prokaryotes, protozoans, algae and higher plants. The FeSOD’s may play a role as antioxidant defense mechanisms in parasitic protozoans, such as Plasmodium falciparum (Pf), which are highly susceptible to superoxide oxidative stress. SOD may have a significant role in the life cycle of this parasite, especially in the erythrocytic phase, where reactive oxygen species can cause the degradation of hemoglobin. Therefore, an evaluation of the Fe-SODs as potential targets to antimalarial drugs was done by bio-informatic analysis. The protein sequences of Cu-ZnSOD1, MnSOD2 from H. sapiens and FeSOD of E. Coli were aligned with that of PfFeSOD in pairs or in three’s. The conserved amino acid residues were compared. The potential proteolytic sites were studied by using peptide cutter software to further confirm the similarity/dissimilarity in the primary structure of the two proteins. In conclusion, this study shows that the PfFeSOD is different from cytosolic Cu-ZnSOD1 of H. sapiens which is likely to be found in the erythrocytes, with just five conserved residues. There were few common proteolytic cleavage sites between the two primary sequences. Hence, the PfFeSOD could be an ideal enzyme to target anti-malarials for this parasite.