Inflammation and activation of the neuroendocrine systems comprise important aspects of stroke pathophysiology. The present study investigated whether baseline plasma brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), cortisol and copeptin levels on admission can predict short-term outcomes and mortality after acute ischaemic stroke. The study group consisted of 189 patients who had their first acute ischaemic stroke. Plasma levels of BNP, NT-proBNP, cortisol and copeptin were evaluated to determine their value with respect to predicting functional outcome and mortality within 3 months. As a result of cardiovascular and neurological investigations (including imaging techniques), lesion size, stroke subtype classification and clinical outcome after 3 months were determined. Plasma levels of BNP, NT-proBNP, cortisol and copeptin were associated with stroke severity, as well as short-term functional outcomes. After adjusting for all other significant outcome predictors, NT-proBNP, cortisol and copeptin remained as independent outcome predictors. In the receiver operating characteristic curve analysis, the biomarker panel (including BNP, NT-proBNP, cortisol and copeptin) predicted functional outcome and death within 90 days significantly more efficiently than the National Institute of Health Stroke Scale (NIHSS) or the biomarker alone. Copeptin showed a significantly greater discriminatory ability as a single biomarker compared to BNP, NT-proBNP, cortisol and NIHSS score. These results suggest that a biomarker panel may add valuable and time-sensitive prognostic information in the early evaluation of acute ischaemic stroke. This may provide a channel for interventional therapy in acute stroke.