Leo Varadkar says it's becoming increasingly clear COVID-19 "will be with us forever".
The Tánaiste says it's looking like it will become an endemic virus that's perhaps "seasonal in nature".
A virus being endemic means it continues to circulate in a particular area or community at a baseline level.
Mr Varadkar today also warned restrictions may yet have to be brought in again.
However, the Tánaiste said he hopes that won't happen this winter.
Speaking in Limerick, he said: "There's always a possibility restrictions may need to be introduced - not just in any particular part of the country, but in the country as a whole.
"What we're aiming to do is to get through this winter without having to do that.
"I think it's increasingly clear COVID is going to be with us forever. It's going to become an endemic virus - perhaps a virus that is seasonal in nature."
Mr Varadkar said everyone in Government and the health service will be "a little bit worried" about what lies ahead in the next few weeks.
He noted: "There does come a point where we have to try to live with this virus.
"That point is now, because we're so well vaccinated as a population."
Earlier, Taoiseach Micheál Martin also said he can't guarantee COVID-19 restrictions won't be reimposed over the winter if cases spiral out of control.
However, he said that advances in COVID-19 vaccines and therapies - as well as increased knowledge of the virus - is "giving us greater capacity to deal with it".
COVID-19 cases have continued to rise in recent weeks, with the five-day moving average of new cases now above 2,000.
While it was confirmed this week that some measures such as COVID passes will remain in place through the winter, today also marks the first time nightclubs have been allowed to reopen in 18 months.