Mutations in common amyotrophic lateral sclerosis (ALS) genes have been reported in sporadic ALS. In the current case, we describe a patient without known family history who was found to harbour a SOD1 mutation (p.D126H variant) and who developed ALS following COVID-19 vaccination. This mutation has only been previously reported once three decades ago in a British family. Although COVID-19 vaccination in itself is unlikely to contribute to the development of ALS, the possibility that vaccination could play a part in triggering the onset of disease in patients with risk variants merits further study.