Background: Hemoglobin E variant results from a G→A substitution resulting consequently in abnormal processing for messenger mRNA. Its interactions with various forms of α and β thalassemia produce a very wide range of clinical syndromes. Methods: A Consent has been taken from a 26-year-old male. CBC, Glucose, Vitamin B12, C-peptide, estradiol (E2), follicle stimulating hormone (FSH), free triiodothyronine (FT3), free thyroxine (FT4), luteinizing hormone (LH), prolactin, parathyroid hormone (PTH), testosterone, thyroid stimulating hormone (TSH) and vitamin D3 (25-OH) and HPLC for hemoglobin separation were performed. Results: There was a history of hemolytic anemia due to infection with malaria and just one blood transfusion. There were no significant clinical findings such as organomegaly, icterus, or thalassemic bone changes. C-peptide, E2 and TSH results were slightly above the normal range. Vit D was slightly insufficient. No Helicobacter pylori Antigen is stool and no clinical abnormalties. All the Hb were abnormal. The patient has low HDL-C which could not be explained. Also the slightly increased hormones of E2 and TSH, the slightly increased C-peptide could not be explained and this requires further investigations. Conclusion: The case was reported as abnormal hemoglobin (Hb E) masking the Hb A2 on HPLC.