Objective The purpose of this concept analysis is to examine the health-related quality of life in children with sickle cell disease. Methods Meleis's concept analysis methodology was followed for analyzing health related quality of life concept. This includes defining the concept, clarifying ambiguities, describing the critical attributes, identifying the observable and measurable empirical referent, delineating the antecedents, the consequences, and modeling to illustrate the concept in its entirety. Articles focusing on quality of life, health-related quality of life (HRQOL) in children with sickle cell disease (SCD) were examined. Results The concept appears well developed and the internal characteristic of HRQOL is delineated. To ensure that its characteristics maintained contextual relevance, a concept called 'fine tune' should be done. Since HRQOL concept is a multidimensional concept, a factor analysis test may be needed to explore the dimensionality and the structure of its meaning. Also, internal consistency reliability needs to be done to assess the items independence of one another. Conclusion Successful patient outcomes is an important goal for nursing and it is critical to health care decision making for practical, ethical, and financial. The analysis of HRQOL concept provided more clarity to the concept definition and also to the underlying outcome measures. Naming the variables of the concepts clearly facilitates comparing and contrasting the healthcare interventions on various patients' outcomes. In addition, by examining the concept in children with SCD, pediatric nurses become more cognizant of the concept's meaning that would easily facilitate the understanding of the children's and their parents' perception of HRQOL.