Ryanair's Michael O'Leary said the airline is "looking at job losses and winter layoffs in Ireland", as a result of poor bookings here compared to other European countries.
Speaking on RTÉ's Drivetime, the group's CEO said bookings have fallen "down by certainly 50%" as a result of the National Public Health Emergency Team's "mismanagement of the situation".
He is calling for quarantine restrictions to be lifted.
Mr O'Leary asked: "Why has Ireland been following unique, closed for business, quarantine restrictions from the 1st of July when almost all other EU countries, like Italy, Germany, the UK are open for business, have allowed intra-EU air travel and now have lower Covid cases than Ireland? NPHET has mismanaged this."
Ryanair is calling on the Government to revise its travel Green List to include countries such as the UK and Germany, which have lower Covid-19 case rates than Ireland.
The airline said this would allow business travel to resume in September.
It said countries such as Germany and Italy, who have an effective test and trace regime, have successfully managed the return of flights between other European countries.
Earlier this week, Ryanair announced that it was reducing the capacity on its flights in September and October because of weakened demand.