Erythropoietin (EPO) is a hypoxia-inducible hormone best known for its role in erythropoiesis. However, EPO also has anti-inflammatory and tissue-protective characteristics in multiple organs as summarised in this review. In the brain, EPO is upregulated by hypoxia, regulates ventilation and plays a key role in neuroprotection and neuroplasticity. Systemically administered EPO crosses the blood-brain-barrier, enhances neuroplasticity and improves cognitive functions in several disorders of the brain. Given this evidence, a trial is being planned to investigate whether EPO can improve the physiologic and neurologic outcome of COVID-19.