Sickle cell anaemia (SCA) is a chronic debilitating condition that has the potential to affect the health-related quality of life (HRQOL) of affected children. It could lead to limitation in physical activity, increased hospital visits, loss of school hours, psychosocial issues and emotional stress. Globally, World Health Organisation estimates that about 300,000 children are born per year with SCD, of which approximately 50% are in Nigeria. In high-income countries, a vast majority of children with SCA survive to adulthood, therefore improvement of their HRQOL is an integral part of the disease management. In low-income settings like Nigeria with the highest burden of SCA in the world, no conscious attempts have been made to assess the HRQOL of affected children. Aim and Objectives: This study aimed to compare the HRQOL of children with SCA with that of age and sex- matched comparison group presenting at Aminu Kano Teaching Hospital. Methodology: It was a comparative cross-sectional study involving children with SCA who attended the paediatric haematology clinic at Aminu Kano Teaching Hospital (AKTH) and age-and sex matched comparison group who were enrolled from the paediatric outpatient department of AKTH. Study participants had a socio-demographic and an anthropometric assessment done, as well as blood sampling for some relevant tests. The HRQOL tool used was the Paediatric Quality of life (PedsQL) generic module, a 23-item questionnaire. It was interviewer administered and parents or caregivers of the study participants and children were required to answer the PedsQL generic module separately. The scores obtained were appropriately transformed and documented, and results anal ysed.