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Scarlets have conceded Saturday's European Champions Cup game at Bristol Bears over the Covid-19 crisis that means the vast majority of their squad are in quarantine in Belfast.
They leave isolation on Friday and player welfare concerns and complications surrounding borrowing players have led to the decision.
Scarlets say they have only 14 fit players in training.
"It is a decision we haven't taken lightly," said chairman Simon Muderack.
"This is a great fixture between two great clubs, which supporters, players and staff on both sides were all looking forward to."
Under competition rules, Bristol will be awarded a 28-0 victory and five match points.
Scarlets had called for tournament bosses to reschedule the game after being caught up in the emergence of the Omicron Covid variant while they were in South Africa for United Rugby Championship (URC) games.
The UK government, backed by the Welsh government, brought in travel restrictions that led to Scarlets flying from South Africa to Dublin, before travelling to Belfast to isolate.
The only squad members to have played since beating Benetton in the URC in October were those involved in Wales' autumn internationals, while a largely shadow team beat Dragons in a friendly on 12 November.
Neighbours Ospreys had been prepared to loan players to Scarlets for the Bristol game.
But European Professional Club Rugby (EPCR) refused to relax rules surrounding the cup-tying of players meaning any loan players cannot also play for another team during the same European campaign.
Scarlets are due to host Bordeaux-Begles on Sunday, 19 December.
In a statement Scarlets said the 14 players in training are made up of seven senior squad members and an equal number of development players.
Muderack said: "The welfare of our players has to be our priority and following discussions with our staff it was felt that there was too much risk to ask the players currently in quarantine to play a game of this magnitude and intensity just a day after coming out of quarantine.
"You have to remember, the squad have been in isolation since the news of this Omicron variant first emerged when they were still in Durban so it will be something like 15 days in all.
"Also, a lot of the players haven't played since the Benetton game on October 22. As a club we have a duty of care to our players."
He added: "We did look into the possibility of registering players from other regions and we have been grateful for the positive response from Ospreys and Dragons.
"But, any players we did loan would effectively be 'cup-tied' and become Scarlets players for the pool stages of the tournament, which has made that option a challenge as well.
"With the integrity of the competition in mind, we felt we were unable to put together a competitive matchday 23 that would be able to take the field against the Bears."
Scarlets are also aware of the situation facing fans who have booked match tickets and accommodation for the fixture.
Muderack added: "I am sure everyone will understand the situation we have found ourselves in through no fault of our own.
"I would also like to stress that we have returned no positive Covid-19 cases in all the rounds of PCR testing prior to leaving and since arriving in South Africa and Northern Ireland.
"We would like to thank everyone at Bristol Bears and EPCR for their understanding of our predicament and look forward to welcoming Pat Lam and his side to Parc y Scarlets for the return fixture in January."
Scarlets say fans will be informed of the plan for those who have booked match tickets and official travel "shortly", an approach mirrored by Bristol.
In a statement EPCR acknowledged "the unfortunate circumstances which have impacted on Scarlets' players and staff through no fault of their own".