Objective: To compare the prevalence of orofacial manifestations between patients with and without sickle cell anemia and to investigate the distribution of such events in patients with sickle cell anemia by sex and age. Method and Material: A cross-sectional study was conducted in which 330 subjects divided into two groups (a group of individuals with sickle cell anemia and a healthy control group) were examined. Results: It was observed that patients with sickle cell anemia had a significantly higher prevalence of previous mental nerve neuropathy (P = .000) and delayed tooth eruption (P = .006) than patients without the disease. Regarding the distribution of orofacial manifestations in patients with sickle cell anemia by sex and age, the only statistical associations were between the prevalence of previous mental nerve neuropathy and sex (P = .023) and previous mandibular pain and age (P = .019). Conclusions: This study found that sickle cell anemia is associated with the prevalence of previous mental nerve neuropathy and delayed tooth eruption. Moreover, previous mental nerve neuropathy is more frequent among females with sickle cell anemia, and previous mandibular pain is more frequent among individuals older than 21 years of age with sickle cell anemia. Further studies using a methodology similar to the one in this study are necessary considering the scarcity of studies using this approach. Keywords: dentistry, epidemiology, sickle cell anemia