Introduction: HbE is the commonest beta haemoglovin (Hb) variant in Southeast Asia. It causes a reduction in synthesis of beta-globin E (βE) chain. Studies indicate HbE coinherited with α-thalassaemia leads to a milder clinical phenotype. This study investigates the concomitant inheritance of α-thalassaemia in Malays with HbE. Methods: Four hundred and fourteen (414) blood samples were screened for haemoglobinopathy using primarily the first 3 steps of the BHES [(B) blood counts, blood film: (H), HPLC; (E),elstrophoresis; (S),stability)] protocol. Complete blood counts were generated on an automated blood cell analyser, HB typing with cation exchange high-performance liquid chromatography (HPLC) and Hb typing with cation exchange high-performance liquid chromatography (HPLC) and Hb electrophoresis at an alkaline pH (pH 8.5). Forty-five (10.9%) were identified as HbE trait and DNA analysis was done for deletional α-thalassaemia using a single-tube multiplex-PCR assay. Results: Among the 45 subjects with HbE trait. 4 (8.9%) were found to have alpha-thalassaemia-2 (α⁺) (α-3.7 kb deletion) and 1 (2.2%) the alpha-thalassaemia-1 (α⁰) (—SEA 20.5kb deletion) defects respectively. Discussion: These findings show that 11.1% of Malays with HbE inherit alpha-thalassaemia concurrently. The most prevalent interaction found was a double heterozygote for HbE/α-thalassaemia 2, followed by HbE/α-thalassaemia 1. Conclusion: Molecular screening of deletional α-thalassaemia identified its concurrent inheritance in 11.1% of Malays who were HbE carriers. This information will guide genetic counseling and the planning of treatment modalities in patients with HbE alpha-thalassaemia.