Objective This study explores how caregiver relationship quality with family, patient, and patient's health care provider (HCP) is associated with subjective caregiver burden during the early treatment phase for late-stage cancer. Method Burden and relationship quality were assessed in telephone interviews with family caregivers (FCGs) of advanced cancer patients. The five subscales of the Caregiver Reaction Assessment measured burden, while relationships were measured with the Family Relationship Index, the Family Inventory of Needs subscale of met needs, and a scale assessing family discord in cancer communication. Results Multiple linear regression analyses in SPSS (v16) of 420 FCGs showed that higher quality relationship with family was associated with lower burden in FCG abandonment, health, scheduling (p<0.001) and finances (p<0.01). Higher quality relationship with patients' HCPs was associated with lower burden in FCG abandonment (p< 0.05), health, and finances (p<0.001). More discordant communication in patient relationship was associated with lower financial burden (p<0.05). Relationship quality was not associated with caregiver self-esteem. Conclusions Findings demonstrate that caregiver relationship quality with family and with HCP are important factors in understanding caregiver burden during the early treatment phase of late-stage cancer care.