This study was conducted to evaluate pregnant women's awareness of sickle cell disease and sickle cell trait and the factors that contribute to it. Two hundred and six pregnant women with at least 20 weeks gestation answered a questionnaire regarding awareness of their trait status and questions to test their knowledge of sickle cell disease. Although the majority of patients were aware of their trait status (87.4%), only 29% of knowledge questions were answered correctly; patients who self-identified as having sickle cell trait did not do better. Patients who responded that they knew a good deal about sickle cell disease scored an average of 3.5 points (number of correct responses to nine questions) more than individuals who responded that they knew nothing (P < 0.001). Individuals who knew they had been tested for the sickle cell trait scored approximately 2 points higher than those who did not know whether they had been tested (P = 0.004). Respondents with at least secondary education scored on average 1 point higher on the knowledge test than those with less education (P = 0.004). Knowing someone with sickle cell disease was associated with a mean score of 1.25 points higher than individuals who did not know any affected individual (P = 0.000).There is a deficit in the knowledge of sickle cell disease among Ghanaian pregnant women. Therefore, there is the need for public education on sickle cell disease.