Sickle cell disease (SCD), an inherited vaso-occlusive disorder, results in recurrent painful episodes and a variety of serious systemic complications that can lead to severe disabilities and even death. Here, we report a case of a 19-year-old African American patient with homozygous sickle cell trait who presented with right upper lid edema and ptosis, 3 days after his admission to the hospital following a sickle cell crisis. Initially, mistaken as a superinfection in the context of his disease, a diagnosis of orbital abscess was made. Intravenous antibiotics and a proper treatment plan were set accordingly. Only after extensive clinical and radiological examinations, it turned out to be an acute subperiosteal orbital hematoma, a rare clinical manifestation of SCD. The aim of our case report was to highlight the difference in orbital presentation between osteomyelitis and subperiosteal hematoma, as well as spreading awareness among medical professionals and especially ophthalmologists for this rare presentation of orbital wall infarction, as the initial differential diagnosis of SCD patients with ocular involvement.