Introduction: Sickle cell disease (SCD) is a genetic disorder with an estimated 5,200 live births each year is a major public health problem in India. Although SCD has been described in India in numerous ethnic groups, it is most prevalent in tribal community. Prevalence of Sickle Cell gene is 5 to 34 % in tribal community, who have a high prevalence of socio-economic disadvantage and are frequently medically underserved. Objectives: The present study was conducted with the aim of assessing QOL and to explore specific domains or factors that are most affected in individuals with sickle cell disease with respect to normal people. Methods: A qualitative case study approach has been employed among 43 SCD affected individuals in age group of 4-48 in 9 villages of Koraput district which is one of the most backward districts of the state and predominantly tribal populated one. The villages were selected accordingly the availability of SCD patients in that village. More priority was given to those villages which have more numbers of SCD patients and more remote, where medical facilities are not easily assessable. Among the selected sample (n=43), children (n=15), where all of them were students, were separated for a categorized study. The quality of life (QOL) was assessed using multidimensional interviews and schedules. Subsequently, Scoring Scales were developed and modified for an intensive study. Results: Result reveals that all factors like physical, psychosocial and cognitive were affected. Their everyday activities like working or schooling, vocational achievement perception, entertainment and participation in cultural activities, and socio economic factors were also affected. Most of the time they feel sad, scared and disinterest. The intensity of weakness and pain was greater in SCD patients as compare to the normal children. Conclusion: Over all QOL is affected in individuals with sickle cell disease (SCD). Interventions to improve QOL should target the affected items. Improving awareness of the disease and its manifestation will help to alleviate the psychosocial affliction of individuals with SCD.