Distance caregivers (DCGs), those who live more than an hour away from the care recipient, often play a significant role in patients’ care. While much is known about the experience and outcomes of local family caregivers of cancer patients, little is known about the experience and outcomes of distance caregiving upon DCGs. The purpose of this study was to identify the relationships among stressors (patient cancer stage, anxiety, and depression), mediators (DCG emotional support and self-efficacy), and burden in DCGs’ of patients with cancer. This study was a descriptive cross-sectional study and involved a secondary data analysis from a randomized clinical trial. The study sample consisted of 314 cancer patient–DCG dyads. The results of this study were: (1) 26.1% of DCGs reported elevated levels of burden; (2) significant negative relationships were found between mediators (DCG emotional support and self-efficacy) and DCG burden; and (3) significant positive relationships were found between patient anxiety, depression, and DCG burden. The prevalence of burden in DCGs, and its related factors, were similar to those of local caregivers of cancer patients, which suggests that interventions to reduce burden in local caregivers could be effective for DCGs as well.