A young man with a rare unstable haemoglobinopathy presented with a high fever, worsening shortness of breath and abdominal pain. At triage his pulse oximetry (SpO2) suggested that his blood oxygen saturation was 84% at room air. However, an arterial blood gas (ABG) oxygen saturation reading (SaO2) was 100%. The significant disparity between the two measurements demonstrates that using pulse oximetry in some unstable haemoglobinopathies may significantly underestimate the actual reading. This error is most probably due to the structural differences in the variant haemoglobin causing light to be absorbed at a different wavelength beyond the normal range of the oximeter. Haemoglobinopathies affect about 7% of the world's population and is often asymptomatic; so, there may be many more undiagnosed cases. Therefore, clinicians may confirm low SpO2 readings with an ABG and, where there is significant disparity with no obvious extrinsic cause, they should consider haemoglobinopathies.