SummaryPurposeAutoantibodies to specific neurologic proteins are associated with subacute onset encephalopathies, which often present with seizures that are poorly controlled by conventional antiepileptic drugs (AEDs). Previous cross‐sectional studies have found specific neurologic antibodies in a small proportion of people with established epilepsy, but these investigations have seldom included patients with recent diagnosis.MethodsWe screened two large epilepsy cohorts to investigate the prevalence of multiple autoantibodies in adult patients with either established or newly diagnosed, untreated epilepsy.Key FindingsEleven percent of patients had antibodies to one or more antigen: voltage‐gated potassium channel (VGKC) complex proteins (5%), glycine receptors (3%), and glutamic acid decarboxylase (GAD) and N‐methyl‐d‐aspartate (NMDA) receptors (1.7% each). There was no difference in the prevalence of antibodies, individually or collectively, between patients with established and newly diagnosed epilepsy or with generalized or focal epilepsy. There was, however, a significantly higher prevalence of positive antibody titers in patients with focal epilepsy of unknown cause than in those with structural/metabolic focal epilepsy (14.8% vs. 6.3%; p < 0.02). Newly diagnosed antibody‐positive patients were less likely to achieve adequate seizure control with initial treatment than antibody‐negative patients, but this difference failed to reach statistical significance.SignificanceThe presence of autoantibodies is equally common in newly diagnosed and established epilepsy, it is therefore unlikely to be an epiphenomenon of long‐standing refractory seizures.