Coronavirus disease 2019 (COVID-19) infections can cause many complications, including central nervous system (CNS) complications. One of the most common COVID-19 CNS complications is COVID-19 encephalopathy, a disorder characterized by cognitive impairment, altered consciousness, and even seizures. The Moderna COVID-19 vaccine is a recently approved mRNA-based vaccine aimed at preventing COVID-19 infections and their complications. Here, we describe two patients with no known neurological or psychiatric history who presented with encephalopathy and seizures that began after part one of their Moderna COVID-19 vaccine series. To our knowledge, there are no other reports of post-Moderna COVID-19 vaccine encephalopathy in the literature. We suggest a mechanism for this complication and thoroughly discuss why the Moderna vaccine is possibly responsible, by addressing confounders in our patients.