The United Rugby Championship (URC) match between Ospreys and Dragons scheduled for 26 December has been called off because of Covid-19.
Ospreys have recorded 18 positive cases, including the Omicron variant.
It is the second match to be called off involving the region after the Heineken Champions Cup trip to Paris to face Racing 92 on 18 December.
Ospreys conceded a 28-0 result and five match points after forfeiting the European match.
A URC statement read: "A number of positive Covid-19 cases within the Ospreys squad have been reported by the region.
"The URC Medical Advisory Group has liaised with Ospreys, who are working with Public Health Wales, and deemed that the fixture cannot go ahead as scheduled."
The tournament organisers will try to fix an alternative date for the fixture.
"At this point there is no impact on Ospreys' R9 fixture with Scarlets, scheduled for Saturday, 1 January, 2022," added URC.
An Ospreys statement read: "While we are disappointed with this outcome, we understand the health and well being of our people, supporters and our opponents and their supporters must be a priority during these unprecedented times.
"Since the start of the pandemic, the Ospreys have followed a high frequency testing regime for all players and staff to minimize the risk of transmission in the workplace, abiding by all the Welsh government health guidelines, and last week was no different.
"The whole Ospreys squad underwent the normal LFT's on Thursday and were cleared to train, but when the PCR test results from that same testing session came through late on Thursday evening 10 members of staff returned positive results, with a further eight testing positive from PCR tests completed on Friday.
"Further analysis of the positive tests confirmed we are dealing with the Omicron variant.
"We have always held ourselves to the highest public health standards and have done everything we can to ensure the safety of our staff and supporters. All of our squad and staff are fully vaccinated.
"Unfortunately, we find ourselves in this situation and all of our players and staff have now been told to self-isolate over Christmas until 27 December.
"We intend to fulfil our fixture with the Scarlets on 1 January."
Cardiff are due to host Scarlets in a URC derby on 26 December at the Arms Park in front of BBC Sport Wales' Scrum V cameras.
The Ospreys-Dragons game is the latest 2021 Welsh festive fixture to fall foul of the pandemic with football matches involving Cardiff City and Newport County already affected.
Welsh sport is also awaiting a decision from the Welsh government over whether any restrictions will be imposed in attempts to fight the Omicron Covid variant.