Background: Hyponatremia induced by syndrome of inappropriate antidiuretic hormone secretion (SIADH) was common electrolyte disturbance encountered in critically ill neurological diseases, which has normal or increased fluid volume. Brain natriuretic peptide (BNP), which is released in equal proportion to N-terminal pro-brain natriuretic peptide (NT-proBNP), plays vital roles in regulation of volume status. The relationship between SIADH and NT-proBNP levels in neurological diseases has rarely been reported. Methods: A retrospective cross-sectional study was conducted to analyze plasma NT-proBNP levels in 33 patients with SIADH and 23 controlled eunatremic patients with neurological diseases. Results: Baseline NT-proBNP levels were compared between two groups [SIADH group: median 311 pg/mL, interquartile range (IQR) 110-768 pg/mL] vs. eunatremic group: median 46 pg/mL, IQR, 12-96 pg/mL) (P<0.05). Plasma NT-proBNP levels were markedly increased in hyponatremic patients who had two or more complications than those who had less complication (P<0.05). In SIADH patients, NT-proBNP levels in remission phase were lower to levels at baseline. Furthermore, no death was seen in eunatremic patients, while five SIADH patients died from complications. Conclusions: SIADH had higher plasma NT-proBNP levels and poorer prognosis compared to eunatremic neurological patients. NT-proBNP serves as a biomarker of disease severity while not extracellular volume (ECV) status in critically ill neurological patients.