The steering committee behind the Aer Lingus Football Classic series has reluctantly canceled the 2021 game between the American Universities of Illinois and Nebraska which had been scheduled for 28 August at Aviva Stadium in Dublin.
Most sporting events are currently banned in Ireland under Level 5 COVID-19 restrictions.
Organizers have also canceled 105,000 hotel bed nights that had been reserved for spectators.
The game will instead be played at the University of Illinois home field.
The inaugural Aer Lingus Classic game between Notre Dame and Navy that had been planned for 2020 but was also canceled had been expected to draw 25,000 spectators from the USA.
Backers say the 5-year series - which is funded by the Dublin City Council and Failte Ireland along with Aer Lingus, Grant Thornton and other private investors - will begin in 2022, virus permitting.
Organizers hope to raise sufficient funds to be able to host a Notre Dame home game next year.