AbstractBackground and purposeOzone‐based treatments can be associated with central nervous system toxicity, which we have termed ozone‐induced encephalopathy (OIE). A detailed description of its phenotype is lacking.MethodsThree cases with findings suggestive of OIE are presented, and the literature is reviewed.ResultsCase 1 is a healthy 59‐year‐old man presenting with loss of consciousness, cortical blindness, restlessness, and anterograde amnesia immediately following a cervical ozone‐therapy (OT) session for chronic neck pain. Brain magnetic resonance imaging (MRI) on admission was normal. A follow‐up scan demonstrated a subtle increased T2 fluid‐attenuated inversion recovery signal within the left cerebellum; an echocardiography showed a patent foramen ovale (PFO). Case 2 is a 56‐year‐old woman with history of migraine, PFO, and lumbar pain who presented with headache, bilateral visual impairment, motor dysphasia, and agitation. All her symptoms began immediately after lumbar OT. Her brain MRI was negative. Case 3 is a healthy 27‐year‐old man who complained of vertigo and mild blurred vision 5 min following a cervical ozone injection. His neurological examination and brain MRI were normal. All three patients had full recovery within 48 h. We found eight additional cases of OIE in the literature.ConclusionsOIE should be considered in patients presenting with neurological symptoms in close relation to OT. OIE is likely a novel iatrogenic entity with a complex pathogenesis; it is probably underreported because it mimics other neurological conditions.