ObjectiveIntracerebral hemorrhage carries a high mortality and survivors are frequently left with significant disability. Immunological mechanisms may play an important role in hemorrhage‐induced brain injury, however, research linking these mechanisms with clinical outcome remains limited. We aim to identify serum inflammatory mediators that are associated with outcome after intracerebral hemorrhage in order to translate data from experimental models to a patient cohort and identify potential targets worthy of reverse translation.MethodsA prospective cohort study at two comprehensive stroke centers enrolled patients with spontaneous intracerebral hemorrhage. Peripheral blood was collected at 6, 24, and 72 h from onset. Functional outcome was assessed at 90 days using the modified Rankin Scale (mRS). Serum inflammatory mediators were measured using multiplex ELISA. Multivariable modeling identified serum biomarkers independently associated with functional outcome at 90 days.Results115 patients completed the study. At 6 h after onset, patients with elevated CCL2 had worse mRS score at day 90 (OR 4.07, 95% CI 1.27–13.10, P = 0.02) after adjusting for age, gender, ICH volume, IVH, infratentorial location and NIHSS score. At 24 and 72 h after onset, elevation in CXCL10 was independently associated with worse 90 days mRS score (24 h: OR 8.08, 95% CI 2.69–24.30, P < 0.001; 72 h: OR 3.89, 95% CI 1.12–13.49, P = 0.03).InterpretationAcute and subacute elevations in specific immune factors are associated with poor outcome, highlighting potential pathways that may contribute to ongoing brain injury in patients with intracerebral hemorrhage.