A high-performance liquid chromatography (HPLC) method designed for the measurement of haemoglobin (Hb)A(1c) in blood was investigated for use as a screening method for the presence of HbS in blood. In the Bio-Rad VARIANT II HbA(1c) method, HbS was found to have a specific retention time and percentage Hb value that enabled the detection of HbS in blood. Other Hb variants did not have the same combination of retention time and percentage Hb as HbS. The HPLC method was superior to the HbS solubility test in ease of performance and readability. Also, the proposed method showed less interference than the solubility test and could be used with samples from all age groups. The proposed method takes 3 min per sample to perform and is thus suitable for large-scale screening.