Sickle-cell disease (SCD), which involves morphological changes to the red blood cells, is the most common hemoglobinopathy worldwide. This conformational change in erythrocytes affects multiple organs and systems, including the hard and soft tissues of the stomatognathic system. The objective of this study was to provide a description of the maxillomandibular positioning of patients using computed tomography in a case series of 40 patients with SCD. To define the facial profile of patients, 2-dimensional (2D) and 3-dimensional (3D) McNamara and Steiner cephalometric tracings were performed. The results showed that there is a tendency to maxillary protrusion in 2D and 3D analyses. There was no statistical difference between the 2D and 3D evaluations; additionally, sex affected the maxillomandibular positioning of patients, but only in McNamara evaluations.