Research indicates that youths with SCD experience increased levels of pain-related anxiety and executive functioning impairments, even in the absence of stroke. Research also indicates that pain and anxiety predict executive functioning and that anxiety might mediate the relation between pain and executive functioning difficulties. The current study sought to evaluate the direct associations among pain, anxiety, and executive functioning, and to examine whether anxiety mediates the relation between pain and specific executive functioning impairments in a sample of youths (age 10 to 19 years) with SCD with no history of stroke. Findings did not support the hypothesis that pain-crisis frequency and anxiety predict executive functioning. Further, they did not indicate that anxiety mediated the relation between pain-crisis frequency and executive functioning.