Background: SCT is a potentially curative therapy for patients with hematologic malignancies that involves prolonged hospitalization, intensive follow-up, and a considerable risk of morbidity and mortality. Family and friends caring for SCT recipients experience substantial caregiving burden as they prepare for SCT. Previous research demonstrates caregiver distress is highest pre-transplant and is comparable to or higher than patient-reported distress. However, the extent of this distress and its relationship to certain domains of quality of life (QOL) and caregiving burden is currently unknown. Methods: We conducted a secondary analysis of cross-sectional data from two supportive care studies focused on caregivers of SCT recipients. Caregivers completed the Hospital Anxiety and Depression Scale (HADS) and the CareGiver Oncology QOL questionnaire to assess their psychological distress and QOL prior to SCT. Scores >8 on the HADS anxiety and depression subscales indicated clinically significant symptoms. We selected eight domains from the CareGiver Oncology QOL questionnaire including social support, physical wellbeing, self-efficacy, coping, leisure time, financial stability, private life concerns, and caregiving burden. Multivariate regression models adjusted for age, sex, caregiver relationship, and SCT type were used to examine associations between these domains and caregivers’ anxiety and depression symptoms. Results: A total of 193 caregivers (age M= 57 years, 70% female, 52% allogeneic transplant) were enrolled with a majority caring for their spouse (80%), parent (8%) or child (5%). Overall 47% and 16% of caregivers reported clinically significant anxiety and depression symptoms, respectively. Low social support, physical well-being, coping and leisure time as well as high caregiver burden, private life concerns and financial distress were associated with both caregiver anxiety and depression symptoms (p < .05). Low self-efficacy was associated with higher anxiety symptoms (p < .05). Conclusions: Caregivers of SCT recipients experience substantial anxiety and depression symptoms prior to SCT. Impairments across multiple QOL domains are associated with caregiver’s psychological distress. Psychosocial interventions designed to improve coping, reduce caregiving burden, and enhance QOL are needed for caregivers prior to transplant.