While survival rates from sickle cell anaemia (SCA) continue to improve, the same cannot be said about the health-related quality of life (HRQoL) which is a useful indicator of a person’s overall well-being. Poor quality of life (QoL) poses a huge emotional, and psychosocial health burden on both the child and their caregivers. Sickle cell anaemia has negative implications to the physical and psychosocial well-being of the sufferers. The negative psychosocial impact of SCA, such as poor QoL, low self-esteem, psychological maladjustment, and stigmatisation, however, has not received sufficient attention as do the physical symptoms. Only few studies in Nigeria have assessed the QoL of children with SCA despite Nigeria accounting for about 50% of the global burden of SCA. Furthermore, in the few studies done in Nigeria, it is unclear if caregivers’ report of the child’s HRQoL could approximate the child’s assessment of his/her HRQoL. Aim and Objectives: The study aimed to assess the HRQoL of children with SCA, determine the correlation between child-reported and proxy-reported HRQoL of the children with SCA; and identify the sociodemographic and sickle cell related determinants of the HRQoL of children with SCA.Subject and Methods: The study was a comparative cross-sectional study of the HRQoL of children aged 5-17 years with SCA and their proxy, and age and gender-matched children without SCA and their proxy. Study data were collected over six months (9thMay 2019 to 8Th December 2019) with a break in August and September because of school holidays. Health quality of life was assessed using the child-reported and proxy- reported versions of the PedsQL™ version 4.0 generic core scale questionnaire. In addition, caregiver’s psychological distress was assessed using the General Health Questionnaire (GHQ). The HRQoL of children with SCA was compared with that of children without SCA. Similarly, the linear relationship between the child’s HRQoL reported by child and by the caregiver was also determined using Pearson’s correlation. Further analysis (Mann-Whitney U or Kruskall-Wallis tests where appropriate) was used to identify determinants of HRQoL of children with SCA.