A young Arab woman with sickle cell-β0-thalassemia disease developed acute colonic pseudo-obstruction that became chronic but showed some response to hydroxyurea. There was no evidence of microvascular or macrovascular occlusion. We also report the case of an Arab man with sickle cell anemia who presented with acute colonic pseudo-obstruction from which he recovered completely within a few days. Although the development of pseudo-obstruction in these two cases seems to have been a complication of sickle cell anemia, its pathogenesis remains unclear. There are several reports of ischemic and inflammatory disorders of the colon complicating sickle cell disease; however, these two cases represent the first descriptions of large-bowel pseudo-obstruction in this hemoglobinopathy.