Advances in antimicrobials and supportive therapy enable most individuals who acquire bacterial meningitis to survive the acute episode. Nonetheless, many survivors suffer neurocognitive complications, often caused by the host’s response to central nervous system (CNS) infection. A key goal of investigating bacterial meningitis in the laboratory is to identify the fundamental drivers of pathologic neurocognitive outcomes. Antibiotic treatment models in which animals survive the initial infection allow investigators to study the long-term consequences of infection, as well as early host responses. The protocol described here mimics the clinical scenario of patients being treated for, and surviving, what would otherwise be a fatal Listeria monocytogenes infection. In this model, C57BL/6J mice are infected intraperitoneally with 2–3 LD50 L. monocytogenes. CNS invasion by bacteria and leukocyte influxes into the brain are typically detectable 48 h postinfection. At that time, mice are treated with ampicillin, the same antibiotic used for human infection. A 14-day course of antibiotics is used to eliminate L. monocytogenes from the brain and peripheral organs, as well as to clear it from the gastrointestinal tract. Treated mice can be observed and studied for an extended period of time to meet diverse experimental objectives, such as analyzing the kinetics of host neuroimmune responses, assessing neurocognitive outcomes, or evaluating the effects of therapeutic interventions on key physiological measurements.