Little is known about the association between cognitive dysfunction among informal caregivers and patients' plans and preferences for patients' end of life care. We report on the frequency of cognitive dysfunction among both patients and caregivers and examine associations between caregivers' cognitive screening scores and end of life plans and preferences of patients with advanced cancer. The current sample was derived from a National Cancer Institute- and National Institute of Mental Health-funded study of patients with distant metastasis who had disease progression on at least first-line chemotherapy, and their informal caregivers (n = 550 pairs). The Pfeiffer Short Portable Mental Status, a validated cognitive screen, was administered to patients and caregivers. Patients were interviewed about their end of life plans and preferences. Logistic regression models regressed patients' advance care planning and treatment preferences on caregivers' cognitive screen scores. Patients' cognitive screen scores were included as covariates. Most caregivers (55%) were spouses. Almost 30% of patients scored worse on the cognitive screen than their caregivers and 12% of caregivers scored worse than the patients. For each additional error that caregivers made on the cognitive screen, patients were more likely (AOR = 1.59, p = 0.002) to report that they preferred that everything possible be done to keep them alive and were less likely (AOR = 0.75, p = 0.04) to have a living will or a health care proxy/durable power of attorney. Worse caregiver cognitive screening scores were associated with higher likelihood of patients' reporting that they wanted everything done to save their lives and a lower likelihood of having a living will or other type of advanced care plan. Future studies should confirm these findings in other populations and determine the mechanisms that may underlie the identified relationships.