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Background: Animal models have demonstrated the deleterious contribution that immunocytes from the spleen exert on secondary brain injury after stroke. While previous work has demonstrated that there is splenic contraction (SC) in patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH), no clinical studies have connected the systemic inflammatory response syndrome (SIRS) with SC. We aim to associate SIRS and its individual components with SC in acute strokeMethods: This is a retrospective analysis of a previous prospective observational study where daily spleen sizes were evaluated in 178 acute stroke patients in a tertiary care center from 2010-2013. Spleen contraction was defined compared to previously established normograms of healthy volunteers from the same study. SIRS was defined as the presence of 2 or more of the following: body temperature <36 or >38C, heart rate >90 beats, respiratory rate >20, and serum white blood cell count >12,000 or <4000 mm3 in the absence of infection. SC was evaluated in patients at 24 and 72 hrs after AIS with SIRS as a primary outcome.Results: 91 patients had verified AIS without concurrent infection at admission and 70 of these patients remained inpatient at 72 hrs. SIRS was not associated with admission SC at 24hr and 72 hrs. Patients with SIRS at 24 and 72 hrs were more likely to have higher admission NIHSS. SIRS was associated with higher discharge mRS (OR 4.24, 95% CI 1.64-10.9, p=0.0028) and PEG placement (OR 3.70, 95% CI 0.95-15.11, p=0.05). 16 patients (22.9%) developed SIRS by 72hrs, only 5 of whom had SC initially. 28 patients (47%) had SIRS on admission that persisted, 12 of whom had SC. SC was not associated with SIRS at 72 hrs (OR 1.05, 95% CI 0.35-2.79, p = 0.92). 14 patients (15%) developed infections while hospitalized, of which 85% had SIRS on admission.Conclusion: Based on our initial evaluation, SC detected within 24 hrs of stroke onset is not associated with SIRS suggesting that the relationship between the two may be more complicated in humans. Consistent with prior studies, however, SIRS is associated with worse outcome. Further studies and additional time points are necessary to further clarify the role of the spleen in the development of SIRS in stroke patients.