Compliment activation has been implicated in Delayed Hemolytic Transfusion Reaction (DHTR) in patients with sickle cell disease, and eculizumab has been reported as an effective treatment for patients with DHTR. Previously reported patients with SCD and DHTR responded well after few doses of eculizumab. We report on the long-term use of eculizumab in a pediatric sickle cell patient with DHTR who had a slow and less sustained response. Long-term use of eculizumab in this SCD patient was effective and well tolerated.