BACKGROUND: Guillain-Barré Syndrome (GBS) is an acute autoimmune polyneuropathy. Cases of GBS have been reported following administration of the vaccines for swine influenza, seasonal influenza, hemagglutinin type 1 and neuraminidase type 1, and meningococcal disease. Despite these links, a causal relationship has not been confirmed. CASE PRESENTATION: We present a case of a 70-year-old woman who presented with progressive bilateral ascending weakness and numbness and reported receiving the first dose of the Moderna COVID-19 vaccine 2 weeks prior to presentation. CONCLUSION: At the time of writing, this is the first reported case of GBS following the Moderna Spikevax COVID-19 vaccine. While a temporal link does not confirm causation, vigilance for GBS symptoms in recently vaccinated patients is crucial. Early recognition enables timely treatment, preventing severe complications like respiratory failure. However, the public health benefits of vaccination far outweigh the risks, as it remains the most effective tool in preventing severe disease.