Purpose: Given the complexities and risks of allogeneic HCT, patients and their family caregivers may experience elevated psychological distress, including symptoms of anxiety and depression, in anticipation of the procedure. Patients and caregivers also bring with them their pre-HCT experiences of diagnosis, prior treatment, and associated burdens, thus potentially compounding their acute distress. Identification of clinical, psychosocial, and sociodemographic factors related to pre-HCT distress would allow targeting of patients and caregivers who may require assistance during the HCT process. Methods: Consecutive patients (n = 111) and their caregivers (n = 110) completed measures of anxiety, depression, cancer distress, perceived threat, perceived control, self-efficacy, relationship quality, and physical quality of life in the week before HCT. Multivariate linear regression analysis was used to identify factors associated with patient and caregiver anxiety or depression, including disease type, donor type, and patient and caregiver sociodemographic, health-related, and psychosocial factors. Results: Family caregivers had higher levels of anxiety and depression symptoms than patients. Thirty percent of caregivers vs. 17% of patients met criteria for clinically significant anxiety and a lesser amount (5% for both) met criteria for clinically significant depression. Patient anxiety was related to younger age (b = - 0.22, p = 0.005) and greater cancer-related distress (b = 0.59, p < 0.001), while caregiver anxiety was related to lower self-efficacy (b = - 0.19, p = 0.011) and greater cancer-related distress (b = 0.58, p < 0.001). Similarly, patient depression was related to lower perceived control (b = - 0.17, p = 0.050), greater cancer-related distress (b = 0.34, p = 0.005), and lower physical functioning (b = - 0.26, p = 0.008), while caregiver depression was related to greater cancer-related distress (b = 0.46, p < 0.001). Conclusions: Family caregivers may be more emotionally vulnerable than patients before HCT and in need of additional assistance. Cancer-related distress was the strongest correlate of anxiety and depression in both patients and caregivers, suggesting that distress related to their cancer experience and its consequences plays a major role in their emotional functioning prior to HCT.