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Acute brain ischemia is accompanied by a disruption of low-molecular-weight aminothiols (LMWTs) homeostasis, such as homocysteine (Hcy), cysteine (Cys), and glutathione (GSH). We investigated the redox balance of LMWTs in blood plasma and its influence on ischemic stroke severity and the functional outcome in patients with an acute period. A total of 177 patients were examined. Total and reduced forms of LMWTs were determined in the first 10–24 h. Stroke severity and functional state were estimated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRs) at admission and after 21 days. Patients with high levels of total Hcy (> 19 μM) showed significantly reduced redox statuses of all LMWTs. Patients with low total GSH levels (≤ 1.07 μM) were at an increased risk of higher stroke severity (NIHSS > 10) compared to patients with a total GSH level > 2.64 μM (age/gender-adjusted odds ratio: 4.69, 95% CI: 1.43–15.4). (1) low total GSH level can be considered as a novel risk marker for the severity of acute stroke in conditions of low redox status of LMWTs and (2) high Hcy levels associated with low redox status of LMWTs. [ABSTRACT FROM AUTHOR]