Sickle cell disease (SCD) is an inherited blood disorder, which has a range of symptoms including pain, fatigue, organ damage, and immunodeficiency. Patients are commonly hospitalized for SCD-related difficulties, most frequently for vaso-occlusive pain crises. In other illness populations, social support has served as a protective factor and aspects of social support (e.g., type of peers and communication) may have differential benefits. The overall aim of this study was to examine pain, social support, type of friend communication, similarity of friends, perceived stigma, quality of life, and loneliness in adolescents admitted to the hospital for SCD pain crises. Perceived social support predicted decreased loneliness in the hospital but did not mediate the relation between pain and loneliness or pain and quality of life. Stigma emerged as a consistent predictor of negative outcomes in terms of quality of life, loneliness, and reduction of pain in the hospital. Qualitative data revealed that hospitalization may have neutral, beneficial and negative effects on friendships and these effects may be dependent on how friends react during pediatric patients’ hospitalizations.