Background: The ability to regulate emotion is associated with affective disorders and the experience of pain. However, little is known about emotion regulation in youth with Sickle Cell Disease (SCD), a population that regularly experiences pain and symptoms of depression and anxiety. This study examines the relationship between emotion regulation and symptoms of depression, anxiety, and pain interference in youth with SCD. Methods: Participants ages 8-20 at a university-based pediatric sickle cell clinic completed the Emotion Regulation Questionnaire (ERQ) and the Cognitive Emotion Regulation Questionnaire (CERQ), self-report measures assessing use of emotion regulation strategies. Participants also completed the Patient-Reported Outcomes Measurement Information System (PROMIS), measures for symptoms of anxiety, depression, and pain interference. Multiple regression models tested associations between use of emotion regulation strategies and symptoms of depression, anxiety, and pain interference. Results: Participants were 51 patients with SCD, 30 female and 21 male, with a mean age of 13.02 years (SD = 0.47, mid-max = 8-20). Use of maladaptive emotion regulation strategies was associated with increased symptoms of depression (r = .58), anxiety (r = .45) and pain interference (r = .30) in youth with SCD. Limitations: Potential limitations of our study include small sample size, use of youth self-report measures, and participant selection contingent on the ability to attend an outpatient appointment. Conclusion: Identifying maladaptive emotion regulation strategies in youth with SCD may provide clinicians with targeted pathways for improving emotional and psychological functioning.