The Acting Chief Medical Officer Dr Ronan Glynn, and his Northern Ireland counterpart, have appealed to people to avoid unnecessary travel across the Irish border.
The two men met on Friday morning to review the ongoing COVID-19 pandemic.
It also comes after Donegal entered level three restrictions for three weeks.
In a joint statement, Dr Glynn and Dr Michael McBride appealed to people on both sides of the border.
They said: "Given the current number of new cases in Donegal and neighbouring areas of Northern Ireland in Derry, Strabane and Fermanagh we would appeal to everyone to avoid all but necessary travel across the border.
"It is also recommended that employers on both sides of the border make every effort to facilitate employees to work from home in so far as is possible.
"We realise that for those living in border areas this will not be welcome news but we must prevent further spread of this virus and we can only do so by working together to protect each other."
'Significant' cases in young people
The two medical officers said close collaboration between relevant authorities "will continue and be strengthened" in the coming days, to address "the concerning trend" in case numbers on both sides of the border.
This will include Donegal and Derry, but also in other areas along the border where the profile of the disease continues to evolve.
Dr Glynn and Dr McBride also jointly appealed to the public across the island to continue to follow public health advice to keep themselves and others safe.
They noted specific concern with regard to the "significant proportion" of cases in young people in both Donegal and Derry, and appealed to teenagers and those in their 20s and 30s in particular to reduce their social contacts.
The meeting also discussed the growing prevalence of the virus in both jurisdictions, and underlined the need for "ongoing cooperation" between public health teams under an existing Memorandum of Understanding.