Rural communities often struggle due to a lack of funding, resources, and support, which can put residents at risk for adverse experiences. Merely living within a rural area is considered an influential contributing risk factor for experiencing social isolation and loneliness. Experiences of social isolation and loneliness are classified as major public health concerns due to the damaging effects they can have on mental and physical health. However, little is known about neural responses to social isolation seen in rural residents. Thus, this study aimed to examine the issues rural communities in Oklahoma face, how these communities respond to experiences of social isolation, and how different experiences and behavioral traits affect this response. Electroencephalography (EEG) was used to assess differences in neural activity in response to rejection; while undergoing EEG, healthy adults across rural Oklahoma played a cyberball game specifically designed to elicit acute feelings of social rejection. In addition, a detailed survey was distributed that encompasses many facets of social experience that may influence their response to social isolation. Specifically, adverse childhood experiences (ACEs), resilience, and social support may serve as important factors for explaining differences in these responses. Results suggest that social support, resilience, and childhood trauma play important roles in how an individual responds to rejection. Social support appeared to foster the formation and continuation of a resilient mindset. Resilient and non-resilient individuals responded differently to rejection, further indicating the importance of a resilient mindset. Understanding the interactions between these variables and an individual’s neural response to rejection will inform future studies on rural communities, which may provide more opportunities for improvement within these communities. The use of a multidisciplinary approach allows for a thorough investigation of adverse childhood experiences, resilience, and social support in the context of rural communities.