Dr Tony Holohan has issued a stark warning in a joint message to the nation with Northern Ireland's CMO Dr Michael McBride.
The country's top doctor joined his Northern Ireland counterpart in delivering a statement to the entire island urging people to stay at home.
The public health experts said they were "gravely concerned" after a "surge" in new coronavirus infections.
The statement reads: "As CMOs, we are gravely concerned about the unsustainably high level of COVID-19 infection we are experiencing on the island of Ireland.
"This is having a significant impact on the health of our population and the safe functioning of our healthcare systems.
“Unfortunately, due to the surge of infections we have experienced over the past few weeks, we have seen an increase in mortality figures and our health systems have been placed under immense pressure.
"We are likely to see ongoing increases in hospitalisations, ICU admissions and mortality in the weeks ahead.”
Both Dr Holohan and Dr McBride said they were asking members of the public to only leave home for essential reasons, and avoid all unnecessary journeys, including cross-border travel.
They continued: "Many of the patients admitted to hospital in January have been under the age of 65 years.
"COVID-19 can affect us all, regardless of age or underlying condition. It highlights the need for us all to protect one another by staying at home.
"Not only will you keep yourself and your loved ones safe, but also help to save lives and avoid more preventable COVID-19 admissions to our currently struggling healthcare systems.
"We will continue to work together to protect public health across the island, as we have done throughout this pandemic, but we need everyone to play their part by staying at home and protecting themselves and their communities.”
