Background: Post-stroke fatigue (PSF) is a common symptom that can have debilitating effects. Furthermore, it is cited as one of the worse symptoms by up to 40% of stroke survivors. Numerous risk factors for PSF, including clinical, laboratory, and hormonal variables, particularly thyroid hormones, were investigated. Aim: To assess the prevalence and contributing factors of post-stroke fatigue in AIS patients. Patients and Methods: This prospective cohort study, which included 70 patients with their first-ever AIS, conducted from August 2022 to January 2023 in the stroke units of the Zagazig neurology department. Patients were evaluated using the fatigue severity scale (scale 7-item version) one month after the stroke's onset. At admission to stroke units, routine laboratory and specialized hormonal assays for thyroid function were performed. Results: 16% of our patients reported post-stroke fatigue. Low T3, high TSH, and dyslipidemia were the three most frequently seen predictors. Conclusion: Dyslipidemia and altered thyroid function are linked to post-stroke fatigue, pointing to a potential role for neuroendocrine responses in PSF.