Objective To investigate the status and influencing factors of post-stroke fatigue among rural patients with first-episode ischemic stroke in Henan Province. Methods The demographic information questionnaire，the Fatigue Severity Scale（FSS），the Self-Rating Anxiety Scale（SAS），the Self-Rating Depression Scale（SDS），and the Uncertainty in Illness Scale for Adults （MUIS-A） were used to investigate 407 rural patients with first-episode ischemic stroke in 50 administrative villages in North Henan. Results The fatigue score of patients in rural areas was （4.30±1.61）. Fatigue was positively correlated with anxiety，depression，and uncertainty in illness（r=0.435， 0.405，0.294，respectively，P<0.05）. The results of multiple linear regression analysis showed that medical insurance for urban workers（with reference to the medical insurance for urban and rural residents），whether there is a chronic disease，anxiety，depression and uncertainty in illness were the influencing factors of fatigue in rural patients with ischemic stroke（P<0.05），which can explain 30.0% of the total variance. Conclusion The fatigue of patients with first-episode ischemic stroke in rural areas of Henan Province is relatively serious，and the fatigue status of this population should draw adequate attentions. Corresponding interventional measures should be developed according to the influencing factors to alleviate the fatigue symptoms of the patients.