We report a case of a pregnant woman with a complex hemoglobinopathy who developed a symptomatic anemia at 28 weeks of gestation and was treated with multiple transfusions of type-specific packed red blood cells. Shortly thereafter, she developed a fever and joint pains, along with laboratory values consistent with hemolysis. Timing suggested a delayed transfusion reaction. An extensive evaluation including red blood cell antigen identification and cross-reaction failed to reveal the cause for her hemolysis. Despite her critically low hemoglobin levels, her transfusions were withheld in an attempt to allow the patient to recover conservatively. With this strategy, her hemoglobin remained below her baseline, but her symptoms began to improve. Her laboratory values normalized, and hemolysis was no longer evident. Three weeks later, her hemoglobin levels returned back to her baseline without additional intervention. She went on to deliver a full-term male infant.