The concept of Health-Related Quality of life (HRQOL) of children and adolescents with Sickle cell disease (SCD) is not clearly understood due to the lack of available studies. This review aimed to elucidate various attributes and related concepts of HRQOL in children and adolescents with SCD using Rodgers' (2000) concept analysis framework. A systematic search was performed to identify studies reporting the attributes, antecedents, consequences, surrogate terms, and related concepts of HRQOL in children and adolescents with SCD. The review included 75 articles, including 70 quantitative, two mixed-methods, and three qualitative studies. These were categorized into attributes, antecedents, consequences, surrogate terms, related concepts, and an exemplar of HRQOL in children and adolescents with SCD. The review identified nine important attributes. It includes multidimensional and dynamic concepts, acknowledging the illness, maintaining emotional balance and self-control, coping with the disease, pain management, stigma and discrimination, treatment burden, palliative care and personal resilience. The antecedents were knowledge and attitude toward the disease, self-efficacy, social support, spirituality and spiritual well-being, disease severity, access to healthcare, environmental factors, and financial considerations. The consequences were independence in personal life, improved physical health outcomes, psychological well-being, family and caregiver well-being, improved family, social and peer relationships and social interactions, improved school performance, and improved overall HRQOL and long-term outcomes. This analysis provides an overview of HRQOL concepts related to children and adolescents with SCD, guiding further research into nursing care and clinical practice.