Little is known about health literacy in childhood-onset systemic lupus erythematosus (cSLE) and how health literacy relates to medication adherence and psychosocial outcomes in this high-risk population. The objective of this study was to evaluate health literacy in adolescents and young adults with cSLE and its association with medication adherence and quality of life. Youth 10-24years with cSLE (n = 48) completed the Brief Healthy Literacy Screen (BHLS) and the Newest Vital Sign (NVS) to assess health literacy. Participants also completed validated measures of medication adherence and quality of life. Descriptive analyses were used to determine levels of health literacy. Bivariate correlations were used to evaluate associations between measures of health literacy with adherence and quality of life. A multivariable regression analyses was used to determine if health literacy was a significant predictor of adherence or quality of life, after adjusting for age, sex, race, and household income. Inadequate health literacy was common in this population, with 67% of youth categorized as having inadequate health literacy by the BHLS and 42% by the NVS. Higher medication adherence was associated with a higher BHLS score (r=.36, p = .017). BHLS was also significantly associated with better quality of life (r = 0.31, p = .034). Inadequate health literacy is prevalent among youth with cSLE. Higher health literacy is associated with higher medication adherence and better quality of life, suggesting that attention to health literacy could improve outcomes for this vulnerable population.