AbstractDisease‐specific knowledge allows individuals with sickle cell disease, sickle cell trait, and unaffected family members alike to make informed decisions and support those affected by the condition. The current study assesses how sickle cell knowledge varies by disease status within families affected by sickle cell disease. One hundred seventy‐nine participants from 84 families completed an online survey and telephone interview. Generalized linear models, with generalized estimating equations, were fitted to evaluate differences in both item‐level responses and total scores on the Sickle Cell Knowledge Scale by sickle cell status. Those with negative or unknown sickle cell status scored significantly lower than those with sickle cell disease or trait, despite being related to someone with sickle cell disease (χ2 (2) = 9.72, p = 0.008). Overall, participants performed poorly on items related to sickle cell trait, with limited understanding of autosomal recessive inheritance patterns. The study's findings suggest a need to move beyond patient‐centered approaches to family‐centered education efforts that reach those with sickle cell traits and negative or unknown status. Findings point to knowledge gaps related to sickle cell trait and patterns of inheritance, representing key enhancement areas for future sickle cell education efforts.