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To examine the association between sepsis and the long-term risk of seizures.We conducted a retrospective population-based cohort study using administrative claims data from all emergency department visits and hospitalizations at nonfederal acute care hospitals in California, Florida, and New York from 2005 to 2013. Using previously validated diagnosis codes, we identified all adult patients hospitalized with sepsis. Our outcome was any emergency department visit or hospitalization for seizure. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). To confirm our findings, we used a matched cohort of hospitalized patients without sepsis for comparison and additionally assessed claims data from a nationally representative 5% sample of Medicare beneficiaries.We identified 842,735 patients with sepsis. The annual incidence of seizure was 1.29% (95% confidence interval [CI] 1.27%–1.30%) in patients with sepsis vs 0.16% (95% CI 0.16%–0.16%) in the general population (IRR 4.98; 95% CI 4.92–5.04). A secondary analysis using matched hospitalized patients confirmed these findings (IRR 4.33; 95% CI 4.13–4.55), as did a separate analysis of Medicare beneficiaries, in whom we found a similar strength of association (IRR 2.72; 95% CI 2.60–2.83), as we did in patients ≥65 years of age in our primary statewide data (IRR 2.83; 95% CI 2.78–2.88).We found that survivors of sepsis faced a significantly higher long-term risk of seizures than both the general population and other hospitalized patients. Our findings suggest that sepsis is associated with pathways that lead to permanent neurologic sequelae.