Black patients with chronic kidney disease (CKD) receive more cardiopulmonary resuscitation (CPR) than other racial groups, and knowledge of CPR influences preferences for care. As limited health literacy disproportionately affects Blacks and contributes to disparities in end-of-life (EOL) care, we investigated whether health literacy mediates racial disparities in CPR knowledge. Black and White adult patients with advanced CKD completed CPR knowledge surveys. Health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine. Among 149 patients, Black patients were more likely to have limited health literacy and lower mean CPR knowledge scores than White patients. In adjusted analyses, health literacy mediated racial differences in CPR knowledge. Knowledge of CPR is lower among Black compared with White CKD patients and health literacy is a mediator of this difference. Future CPR educational interventions should target health literacy barriers to improve informed decision-making and decrease racial disparities at the end of life.