Understanding patient experiences, quality of life, and treatment needs in individuals with sickle cell disease (SCD) is essential in promoting health and well-being. We used measures from the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), Patient Reported Outcomes Measurement Information System (PROMIS), and Quality of Life in Neurological Disorders (NeuroQol) to evaluate pain impact, sleep impact, social functioning, depressive symptoms, tiredness, and cognitive function (collectively, patient reported outcomes [PROs]) and to identify associated demographic and clinical characteristics. Participants (n = 2201) between 18 and 45 years were recruited through the eight Sickle Cell Disease Implementation Consortium (SCDIC) sites. In multivariate models, PROs were significantly associated with one another. Pain impact was associated with age, education, employment, time since last pain attack, hydroxyurea use, opioid use, sleep impact, social functioning, and cognitive function (F = 88.74, P <.0001). Sleep impact was associated with household income, opioid use, pain impact, social functioning, depressive symptoms, and tiredness (F = 101.40, P <.0001). Social functioning was associated with employment, pain attacks in the past year, autoimmune/inflammatory comorbidities, pain impact, sleep impact, depressive symptoms, tiredness, and cognitive function (F = 121.73, P <.0001). Depressive symptoms were associated with sex, sleep impact, social functioning, tiredness, and cognitive function (F = 239.51, P <.0001). Tiredness was associated with sex, education, sleep impact, social functioning, depressive symptoms, and cognitive function (F = 129.13, P <.0001). These findings reflect the baseline PRO assessments among SCDIC registry participants. Further research is needed to better understand these outcomes and new targets for interventions to improve quality of life and function in people with SCD.