BackgroundPost-stroke infections may cause sepsis, which is associated with poor clinical outcome. Sepsis is defined by life-threatening organ dysfunction that can be identified using the Sequential Organ Failure Assessment (SOFA) score. The applicability of the SOFA score for patients not treated on an intensive care unit (ICU) is limited. The aim of this study was to develop and validate an easier-to-use modification of the SOFA score for stroke patients.MethodsUsing a registry-based cohort of 212 patients with large vessel occlusion stroke and infection, potential predictors of a poor outcome indicating sepsis were assessed by logistic regression. The derived score was validated on a separate cohort of 391 patients with ischemic stroke and infection admitted to our hospital over a period of 1.5 years.ResultsThe derived Stroke-SOFA (S-SOFA) score included the following predictors: National Institutes of Health stroke scale ≥ 14, peripheral oxygen saturation < 90%, mean arterial pressure < 70 mmHg, thrombocyte count < 150 109/l and creatinine ≥ 1.2 mg/dl. The area under the receiver operating curve for the prediction of a poor outcome indicating sepsis was 0.713 [95% confidence interval: 0.665–0.762] for the S-SOFA score, which was comparable to the standard SOFA score (0.750 [0.703–0.798]), but the prespecified criteria for non-inferiority were not met (p = 0.115). However, the S-SOFA score was non-inferior compared to the SOFA score in non-ICU patients (p = 0.013).ConclusionsThe derived S-SOFA score may be useful to identify non-ICU patients with stroke-associated sepsis who have a high risk of a poor outcome.Supplementary InformationThe online version contains supplementary material available at 10.1186/s42466-023-00258-4.