<b><i>Introduction:</i></b> Circulating neutrophil and lymphocyte levels may be modifiable outcome predictors of ischemic stroke. We sought to compare these immune cell parameters with advanced imaging assessment and the 90-day clinical outcome. <b><i>Methods:</i></b> We used a retrospectively collected cohort of consecutive ischemic stroke patients presenting within 4.5 h of symptom onset who had acute CT perfusion and routine blood collection before treatment with intravenous thrombolysis and 24-hour MRI scanning at the John Hunter Hospital. Full blood counts were performed acutely at 24 h and 7 days. Patient outcomes were assed at 90 days after stroke with the modified Rankin Scale (mRS). <b><i>Results:</i></b> Overall, 142 patients were assessed during the study period. Patients with a poor outcome (mRS 3-6) had increased neutrophils (44% increase, p = 0.016), decreased lymphocytes (7% decrease, p = 0.491) and an increased lymphocyte-to-neutrophil ratio (196% increase, p < 0.001). Patients with good outcomes (mRS 0-2) did not have significant changes in their full blood counts. There was no relationship between the neutrophil count at 24 h and penumbral volume (r² = 0.217, p = 0.212), reperfusion (r² = 0.111, p = 0.085), or core growth (r² = 0.297, p = 0.107). A backward multivariate analysis containing the 24-hour core volume and 24-hour neutrophil count was strongly related to the 3-month outcome (r² = 0.477, area under the curve = 0.902, p < 0.001). <b><i>Conclusions:</i></b> Peripheral neutrophils have potential as a biomarker of outcome when used in conjunction with advanced imaging. Peripherally measured neutrophil counts change significantly over time after stroke and may be potential targets for immunomodulatory therapy in patients with a severe stroke or a large infarct volume.