Anti-LGI1 (Leucine-rich, glioma-inactivated 1) antibody is an autoantibody detected from some patients with autoimmune epilepsy or limbic encephalitis with clinical features of focal seizures and cognitive impairment. In addition, previous study reported that Lgi1-knock out mice exhibited increased susceptibility to seizure induction. In this study, we evaluated the effects of intrahippocampal anti-Lgi1 antibody on cognitive function and seizure susceptibility in mice. C57BL/6J mice were intrahippocampally microinjected with anti-Lgi1 antibody (Abcam). A week later, the novel object recognition test and the seizure susceptibility test against pentylenetetrazol (PTZ, 35 mg/kg, i.p.) were performed. Areas of brain excitation were also evaluated by immunohistochemical analysis of c-Fos expression. While no cognitive impairment was observed, the intrahippocampal injection of anti-Lgi1 antibody showed a tendency to increase the seizure susceptibility to PTZ, as compared to control mice. In addition, analysis of c-Fos expression using mice without seizure showed significant increase in c-Fos expression in cerebral cortex and hippocampal CA3 area of the antibody-injected mice compared to control mice. Anti-Lgi1 antibody may promote the seizure occurrence by enhancing neural activity in cerebral cortex and hippocampus.