Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a new infectious agent causing the ongoing coronavirus disease 2019 (COVID-19) pandemic since December 2019. The most severe disease and mortality due to COVID-19 occur in patients with comorbidities. Sickle cell disease (SCD) patients are considered immunocompromised due to the loss of splenic function. Here we report three cases of COVID-19 in one family affected by SCD. A mother and two siblings were diagnosed with COVID-19. The two siblings, 14 and 12 years, presented with vaso-occlusive crisis and one subsequently developed acute chest syndrome (ACS). All family members had favorable outcomes.