Red blood cell exchange transfusion may be beneficial and should be considered in the early management of patients with sickle cell disease and COVID‐19 to prevent the need for intubation and intensive care unit admission due to respiratory distress.

We present the first documented case of a 69 year-old female with history of sickle cell anemia with hereditary persistence of fetal hemoglobin that presented due to joint pains and COVID-19 infection. The red blood cell exchange transfusion may play an important factor in preventing intubations and longer hospital stays.