Racial discrimination is one of many barriers experienced by African Americans that interfere with health self-care management. Discrimination stress may decrease the tendency for individuals to resonate with the social-emotional appeals embedded in persuasive health information, which are known to play a key role in producing behavior change. Understanding the neurobehavioral underpinnings of discrimination stress experienced by African Americans may help reduce or resolve this important health disparity. The purpose of this secondary analysis was to examine the association between neural processing of health information and perceived discrimination. In particular, we focused on three previously identified measures of health information processing associated with distinct brain areas: analytic network, empathy network, and the ventral medial prefrontal cortex. Data were obtained from 24 African Americans enrolled in a blood pressure self-care management study. Participants completed surveys assessing racial discrimination and global stress, as well as a 40-minute functional magnetic resonance imaging protocol used to measure neural activation associated with processing different types of health information. Discrimination stress was significantly related to reduced activation of the empathy network and ventral medial prefrontal cortex, whereas there was a nonsignificant positive relationship with activity in the analytic network. Uncovering associations between patient experiences, such as racial discrimination, and their neural processing of health information can lead to the development of tailored health messages and self-care management interventions. This may inform strategies to close the gap on health outcomes.