Little is known about out-of-pocket (OOP) costs incurred for medical and health needs by rural breast cancer survivors and what factors may be associated with higher OOP costs and the associated economic burden. Data were examined for 432 survivors participating in the Rural Breast Cancer Survivor Intervention trial. OOP costs were collected using the Work and Finances Inventory survey at baseline and four assessments every 3 months. Mean and median OOP costs and burden (percent of monthly income spent on OOP costs) were reported and factors associated with OOP costs and burden identified with generalized linear models fitted with over-dispersed gamma distributions and logarithmic links (OOP costs) and with beta distributions with logit link (OOP burden). OOP costs per month since the end of treatment were on average $232.7 (median $95.6), declined at the next assessment point to $186.5 (median $89.1), and thereafter remained at that level. Mean OOP burden was 9% at baseline and between 7% and 8% at the next assessments. Factors suggestive of contributing to higher OOP costs and OOP burden were the following: younger age, lower income, time in survivorship from diagnosis, and use of supportive services. OOP costs burden rural breast cancer survivors, particularly those who are younger and low income. Research should investigate the impact of OOP costs and interventions to reduce economic burden.