Background: Sickle cell disease (SCD) is an inherited chronic disease that is characterized by complications such as recurrent painful vaso-occlusive events that require frequent hospitalizations and contribute to early mortality. The objective of the study was to report on the initial measurement properties of the new PedsQL� SCD Module for pediatric patient self-report ages 5�18 years and parent proxy-report for ages 2�18 years. Procedure: The 43-item PedsQL� SCD Module was completed in a multisite study by 243 pediatric patients with SCD and 313 parents. Participants also completed the PedsQL� 4.0 Generic Core Scales and PedsQL� Multidimensional Fatigue Scale. Results: The PedsQL� SCD Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report ??=?0.95; parent proxy-report ??=?0.97), and good reliability for the nine individual scales (patient self-report ??=?0.69�0.90; parent proxy-report ??=?0.83�0.97). Intercorrelations with the PedsQL� Generic Core Scales and PedsQL� Multidimensional Fatigue Scales were medium (0.30) to large (0.50) range, supporting construct validity. PedsQL� SCD Module Scale Scores were generally worse for patients with severe versus mild disease. Confirmatory factor analysis demonstrated an acceptable to excellent model fit. Conclusions: The PedsQL� SCD Module demonstrated acceptable measurement properties. The PedsQL� SCD Module may be utilized in the evaluation of SCD-specific health-related quality of life in clinical research and practice. In conjunction with the PedsQL� Generic Core Scales and the PedsQL� Multidimensional Fatigue Scale, the PedsQL� SCD Module will facilitate the understanding of the health and well-being of children with SCD.