ABSTRACT: Goals: The aims of this study were to determine if the infection rate differs between the first and recurrent ischemic stroke/transient ischemic attack (TIA), if the pattern of the peripheral immune response (PIR) differs between the first and recurrent ischemic stroke/TIA and if infection further influenced the pattern of the PIR. Methods: Retrospective review of 500 stroke cases with strict exclusion criteria (e.g., hemorrhagic stroke, subarachnoid hemorrhage, or spontaneous intracerebral hemorrhage; history of cancer; on steroids or immune suppressive drugs; recent invasive procedure) resulted in inclusion of 198 cases. Independent variables were first stroke or recurrent stroke and not infected or infected cases. Main-effect dependent variables were the white blood cell (WBC) and differential leukocyte counts (percentages of 100 cell counts for neutrophils, lymphocytes, and monocytes and absolute counts of neutrophils, lymphocytes, and monocytes). Findings: Infection rate was not different between the first versus recurrent stroke (p = .279). The pattern of WBC and differential counts were not different between groups, but addition of the covariate of infection showed group differences (p = .05). A four-group comparison of the dependent variables with the laboratory normal ranges showed lymphocyte percentages below the lower range limit in all four groups. Generalized linear modeling showed a modest rise (15%) in WBC counts in both groups with concomitant infection, a modestly low (−18%) lymphocyte percentage in recurrent stroke with infection, and a more substantial rise (22%–26%) in absolute neutrophil count in both groups with concomitant infection. Conclusions: Infection influences the pattern of the PIR in the first and recurrent stroke/TIA, and this difference can be quantified.