Sickle cell anemia (SCA) is a severe form of sickle cell disease that primarily affects black populations and individuals in tropical countries. This condition causes significant morbidity and mortality and leads to a range of psychosocial challenges. A preliminary search was conducted on Ovid Medline and public databases with a combination of Medical Subject Headings keywords, resulting in 368 articles. The articles were screened based on the selection criteria in a nonsystematic method by 3 researchers, and a narrative synthesis was done to analyze extracted data from selected peer-reviewed article. Mental disorders, sleep disturbances, interpersonal relationship challenges, stigmatization, and workplace discrimination were identified as significant contributors to the psychosocial distress experienced by individuals with SCA and their families. Depression and anxiety were prevalent among individuals with SCA, leading to poor treatment adherence, increased pain, and disruptions in various aspects of life. Sleep disturbances, including sleep-disordered breathing and sleepwalking, were also identified as significant contributors to poor sleep quality in SCA patients. Families of individuals with SCA also face challenges, including psychological stress, financial strain, and social disruption. Stigmatization is common, leading to misconceptions and discrimination. Workplace discrimination is prevalent, with a high unemployment rate among adult SCA patients. Comprehensive care is crucial to address these psychosocial issues. Early identification and intervention, comprehensive support programs, patient and family education, enhanced pain management strategies, and integration of mental health into clinical care are recommended. School-based support, research and advocacy, and community support groups are also important. By addressing these challenges through comprehensive care and support, healthcare professionals, policymakers, and society can reduce psychosocial distress and improve the lives of individuals with SCA.