Sickle cell disease (SCD) is a serious and debilitating disease that primarily affects Black and Latinx populations here in the United States; however, it can affect other racial and ethnic groups as well. In the Midwest, compared to the East and West coast, SCD affects a smaller number, at approximately 15,000. For years, there has been a misconception that SCD is only a “Black” disease. This has influenced the treatment, research, and support of the disease. Given that this disease mostly affects minority populations, it is important to assess not only the knowledge of the groups most commonly affected, but also healthcare professionals who are responsible for providing care for these individuals, and other populations who can be catalysts for raising awareness and knowledge about the disease. Five hundred and seventy-three participants were surveyed and 29 participated in focus groups or interviews. Results showed that healthcare professionals and Black Americans were more knowledgeable about SCD than Latinx Americans and other populations. Perceptions among groups were not statistically different and were similar qualitatively. Stigma was impacted by knowledge level; as knowledge levels increased stigma decreased. There were differences found between healthcare professionals and other populations (both had higher levels of stigma than the other two groups). The findings support that knowledge about SCD is needed across all groups, particularly among Latinx Americans, as well as knowledge concerning treatment of SCD for those in the healthcare field. Keywords: sickle cell disease, disease knowledge, disease perception, disease stigma