The Health Minister has intimated that Munster players and staff will have to isolate on their return to Ireland.
On Friday evening they were preparing to leave South Africa after United Rugby Championship organisers postponed the next two rounds of matches scheduled for the country.
Munster were due to play the Vodacom Bulls at Loftus Versfeld on Saturday before a meeting with Emirates Lions in Johannesburg a week later.
A Munster statement on Friday read, "Overall, the training week in Pretoria went well and the squad returned negative PCR test results in this week’s routine testing that had taken place ahead of Round 6."
However, those negative PCR tests will likely not be enough to avoid isolation, giving them a race against time to prepare adequately for their first Heineken Champions Cup pool game away to Wasps on December 12.
Speaking to RTÉ News on Friday, Minister Stephen Donnelly admitted to being concerned by the spread of the South African variant - B.1.1.529, or Omicron as it's officially been labelled.
"The initial indications that we have are that it's highly transmissible," he said, "We've seen in South Africa that it has out-performed - or taken over from - Delta [variant].
"One of the big questions the scientific community are looking at now is, do the vaccines have any different effect? In other words, can it escape the vaccines.
"We don't know that yet, so that's one of the things we're looking to. So, what we're doing is we're acting in a precautionary manner in line with the UK, and in line with the rest of Europe and bringing in measures to immediately address the chances of this new variant being imported to Ireland."
He added, "We don't have any direct flights into Ireland so that's not something we need to look at.
"The travel advice now is 'do not travel' to these seven countries [South Africa, Zimbabwe, Botswana, Mozambique, Namibia, Lesotho, Eswatini] unless it is absolutely necessary.
"The advice to our residents who are in the seven countries is to return as soon as possible, and to comply with new Public Health protection measures we'll have here.
"Probably the most important of those are a pre-flight PCR [test] - regardless of your vaccine status. And when you come back then, mandatory home quarantine with two PCR tests.
"The home quarantine would be for ten days, assuming the second test is not detected."
Minister Donnelly said the Gardaí will have a role in policing the quarantine measures.
Those measures will also apply to the Ireland women's cricket team, who are in Zimbabwe for a World Cup qualifying tournament.