Abstract Introduction Vasculopathy of the large vessels commonly occurs in sickle cell disease, and as a result cerebral infarction is a well characterized complication of this condition. However, spinal infarction appears to be rare. Spinal infarct is infrequent in the non-sickle cell population as well, and accounts for only about 1 percent of all central nervous system infarcts. Case presentation In the present work, we report the case of a 19-year-old African-American man with sickle cell disease who experienced an anterior spinal infarct and subsequent quadriplegia. He was incidentally noted to be a heterozygote for factor V Leiden. We also reviewed the literature and found two previous cases of spinal cord infarction and sickle hemoglobin. Our literature search did not demonstrate that heterozygocity for factor V Leiden plays an important role in spinal cord infarction. Conclusions The paucity of cases associated with sickle hemoglobin does not allow us to postulate any particular risk factors with sickle cell disease that might predispose patients to spinal cord infarction. Our patient’s case raises the question as to whether spinal cord infarction is being missed in individuals with sickle cell disease and neurologic symptoms.