On the assumption that resistance to malaria is related to the structure of the haemoglobin molecule, a comparative study was designed to determine the interaction of antimalarial drug, Fansidar with normal haemoglobin (HbA) at pH 5.0 and pH 7.2 using Fourier Transform Infrared (FTIR) Spectrophotometry in the mid-infrared region (4000-200 cm-1). Fansidar, a combination of Pyrimethamine (Dihydrofolate reductase inhibitor) and Sulphadoxine (PABA inhibitor) is active against the asexual erythrocytic stages of Plasmodium falciparum and may be effective against strains of P. falciparum resistant to chloroquine. Genotype AA blood sample was collected from the University of Nigeria, Medical Centre, Nsukka. The blood was centrifuged and purified to obtain crude haemoglobin A. The crude haemoglobin was dialyzed at 4 oC for 12 hours against 50mM Tris-HCl buffer of pH 7.2. The FTIR results showed that at pH 5.0, in the amide I region (1700 – 1600 cm-1) comprising the proteins secondary structural components (α-helix, β-sheets, random and turn structures), there were significant changes in absorbance for HbA while at pH 7.2, little or no significant change in absorbance were observed. The results suggest that HbA is easily destabilized at pH 5.0, than at pH 7.2, on interaction with Fansidar. These haemoglobin-drug interactions may hinder the development of the Plasmodium falciparum at the intraerythrocytic stage and may account for the novel strategies of monitoring HbA aggregation during malarial infection as well as improvements in administering effective antimalarial treatment. The interaction of Fansidar with HbA at pH 5.0 and pH 7.2 can be likened to the iron-ligand interactions between α and β subunits of haemoglobin. Understanding the interaction of antimalarial drugs with haemoglobin has allowed the identification of essential processes and metabolic weak points that could be exploited to combat this scourge to humanity. Keywords: Malaria, Antimalarial, FTIR, Haemoglobin, ligand, Plasmodium falciparum