Alloimmunization is a common problem in sickle cell disease (SCD) patients. Providing antigen-negative units in this group of patients makes it challenging for the transfusion laboratory. Antibody identification is required to decrease the incidence of hemolytic transfusion reaction in case of alloimmunization. In SCD patients, identification of antibody specificity is essential to prevent particularly delayed type transfusion reactions. This is a case report of a transfusion-dependent SCD patient whose antibody specificity could not be determined on initial antibody identification testing. A modified antibody identification test was done with polyethylene glycol (PEG) and enzyme to identify antibody specificity in this patient. Alloantibody anti-c was identified and reported to the clinician. The patient was transfused with c antigen-negative blood. This case report highlights the role of PEG and enzyme treatment in antibody identification for transfusion support in this group of highly alloimmunized patients.