Neuroinflammation plays an essential role in the pathogenesis of acute ischemic stroke (AIS). This study aims to investigate the predictive value of the systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) on mortality and functional limitation in patients with critical AIS. Patients with critical AIS in a tertiary hospital's intensive care unit (ICU) between June 2020 and 2022 were retrospectively examined. Patients were classified according to their 28-day mortality (survivor and non-survivor group) and functional status (poor and good functional outcomes). The performances of SII and SIRI in predicting mortality and functional outcomes were compared. A total of 198 patients were included in the study. The median age of the entire population was 70 (56-86) years, and 52% (n = 103) were male. Coronary vascular disease/heart failure was found to be significantly higher in the mortality group (p = 0.025). While SII was found to be significantly higher in the mortality group (1,180 vs. 811, p = 0.038), SIRI did not show a significant difference (1.82 vs. 1.70, p = 0.257). SII and SIRI were significantly higher in the poor functional outcome group (p <
0.001 and p = 0.015). In the ROC analysis of the functional status prediction performances of SII and SIRI, the cut-off value of SII was ≥ 1,146, the area under the curve (AUC) = 0.645 (0.568-0.722), the cut-off value of SIRI was ≤ 2.54, AUC = 0.600 (0.520-0.680) was detected. SII helps predict 28-day mortality in patients with critical AIS. Both SII and SIRI can predict functional status at discharge.