Chronic pain is a major feature of sickle cell disease (SCD) and negatively impacts physical and psychosocial function in affected youth. Self-management is an important and critical tool that can improve the long-term outcomes in SCD and help reduce healthcare utilization and facilitate transition to adult care for this patient population. A better understanding of which youth with sickle cell disease have poorer self-management skills as well as the factors associated with self-management can help inform targeted interventions to address this area of focus. Patient activation refers to a person’s knowledge, skills, and confidence to self-manage their health conditions, and can be assessed with self-report tools. The overarching objective of this study was to assess patient activation among youth with sickle cell disease at baseline, while enrolled in a multicenter randomized controlled trial (RCT) of an mHealth (mobile health) pain self-management intervention. In this cohort of 100 youth with SCD, 60% had high PAM levels. We found that high patient activation was significantly associated with greater self-efficacy, passive coping, and perceived social support. We found that low patient activation was associated with fatigue, poorer executive function and poorer physical function. Our study cannot conclude causality or directionality of the psychosocial resilience factors associated with PAM levels. Nonetheless, our findings suggest potential areas to target to help build patient activation in youth with SCD. Next steps for our team include assessing changes in PAM levels longitudinally and evaluating whether PAM levels moderate intervention effects and/or improve via receipt of the mHealth intervention of interest.