This study investigated the temporal relationship between pain and sleep in children with sickle cell disease (SCD) and examined the influence of additional stressors and pain medication practices on this relationship. To accomplish the goals of the study, 20 children with SCD aged 8 to 12 years of age completed daily diaries for approximately 5 weeks. These diaries were analyzed using multilevel models. Results were consistent with the hypothesis that there is a cyclic relationship between high SCD pain and poor sleep. Specifically, high levels of daily SCD pain were significantly related to poor sleep quality that night. Also, poor sleep quality during the night was significantly related to high SCD pain that day. Poor sleep quality appeared to be the stronger predictor in the pain-sleep cycle. Additional stressors and pain medication use did not evidence a substantial impact on the relationship between SCD pain and sleep, but instead evidenced more direct influences on SCD pain and sleep aspects. Clinical and policy implications include the possible benefits of raising awareness among clinicians, policymakers, patients, and their parents about the interaction between the child's symptoms and sleep patterns. Additional research should study how other disease symptoms may influence sleep and how sleep may influence other disease symptoms. In addition, this research should examine the role of disease management strategies implemented by the child and his/her family on these relationships.