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Background and Purpose: Negative outcomes of stroke are associated with poorer quality of life (QoL) and impact stroke recovery. The purpose of this study was to characterize QoL and loneliness in a sample of rural Appalachian stroke survivors within 1 year of stroke. Methods: Using mail survey methodology, survey data were collected from 121 ischemic and hemorrhagic stroke survivors living in West Virginia using 13 subscales from the Neuro-QOL survey and the three-item UCLA Loneliness Scale. Statistical Package for Social Sciences v. 20 was used to conduct descriptive, comparative, and predictive analyses. Multiple linear regression models were used to assess explanatory value of loneliness for QoL domains while controlling for comorbidities. Results: Participants who were discharged to a nursing home had poorer QoL when compared with those who were discharged to home. Stroke survivors who continued to smoke were less satisfied with social roles and reported higher mean loneliness and depression scores. History of psychological problems negatively correlated with all QoL domains and loneliness scores. Loneliness predicted poorer QoL even when controlling for age, gender, and significant comorbidities. Conclusion: Nurses need to assess for loneliness, include loneliness in care planning, and implement smoking cessation and cognitive behavioral interventions. Interventions that target loneliness for stroke survivors could potentially diminish psychological sequelae after stroke and enhance QoL.