The US blood donor pool does not reflect the multicultural nature of the country. Diverse communities have not been effectively engaged to donate blood in a culturally competent manner. For patients with sickle cell disease, the majority of whom are Black, blood donors of African ancestry have a higher likelihood of being a match. Latinos have the highest prevalence of individuals with type O blood, which is in high demand. Engaging underrepresented populations to donate blood requires building trust, developing cultural understanding, and partnering with trusted organizations as an investment into the community.