Pulse oximetry normally provides a reliable indicator of arterial blood oxygen saturation. Individuals with a variant hemoglobin with low oxygen affinity would exhibit pulse oximetry values consistent with hypoxemia despite maintaining adequate oxygen delivery to tissues. We describe a patient we diagnosed with hemoglobin Rothschild and his mother. He presented with SpO2 81% on pulse oximetry and PaO2 on arterial blood gas of 47 mm Hg, while his mother had SpO2 87%. These values were significantly lower than physical examination suggested. A possible dyshemoglobinemia should be suspected when discordance exists between pulse oximetry readings and physical examination findings.