Asymptomatic patients with hemoglobin (Hb) variants can be detected by low oxygen levels in pulse oximetry (SpO₂). Depending on the type of Hb variant, low SpO₂ values are either falsely low, with corresponding normal arterial oxygen saturation (SaO₂), or truly low, with low SaO₂ values, as observed in Hb variants with low oxygen binding affinity. In this context, attention must be paid to the method of determining SaO₂. Low oxygen affinity Hb variants such as Hb Rothschild (HbR) might compensate for low oxygen loading in the lung through unloading more oxygen in peripheral tissues. This is the first case report to illustrate that maximal oxygen uptake and the workload are unimpaired in HbR variant patients.