Sickle cell disease (SCD) is a common genetic disorder affecting up to 2.6% of the population in Saudi Arabia. SCD results in severe disability, reduced quality of life, extensive use of medical resources, increased economic burden, and a high likelihood of increased mortality. Red blood cell transfusion remains a cornerstone in the management of SCD complications. This position paper highlights the current state of SCD management within the Kingdom of Saudi Arabia. Despite the advantages of automated red blood cell exchange (aRBCX) and guideline recommendations, its use remains limited. In practice, aRBCX is used for a variety of indications, including acute management and prophylaxis of stroke, systemic fat embolism, severe forms of acute chest syndrome, preoperative management, hematopoietic stem cell transplantation, hepatic crisis, and priapism. However, aRBCX is underutilized in pregnancy. Common gaps identified by the advisory panel include the absence of standardized national guidelines, limited access to aRBCX, issues with vascular access, lack of equipment, and insufficient staff training. Another limitation to the use of aRBCX is the higher blood requirements compared to other blood transfusion modalities. These factors contribute to geographical disparities in the management of SCD and suboptimal patient outcomes. To address these issues, the advisory panel recommended developing and implementing evidence-based national guidelines, expanding access to aRBCX, enhancing health staff education and training, and establishing a robust national SCD registry. By prioritizing these recommendations, we can help streamline SCD care, reduce practice variation, and nationalize sickle cell disease management in Saudi Arabia to improve patient care.