Saturday's East Midlands derby between Northampton and Leicester has been cancelled after a number of positive" coronavirus tests in the Saints camp.
In addition to the confirmed cases, "further players" are also having to isolate as close contacts.
Saints - whose last Premiership fixture at London Irish was also called off - will not train again until Monday.
The game will not be rescheduled, with a Premiership Rugby panel deciding the allocation of points "in due course".
"We are incredibly disappointed and frustrated that we are unable to proceed with such an important fixture for the club," said Northampton director of rugby Chris Boyd.
Five Premiership games have now been cancelled this season because of Covid-19 outbreaks and there have also been more positive tests at champions Exeter this week, although they still expect their match against Bristol to go ahead on Saturday.
In the previous four instances, the team affected by the virus were awarded two points and a defeat by a Premiership panel, with their opponents given four points and a win.
Premiership Rugby has published additional Covid-19 protocols around matchdays and training to make the league "even more Covid safe", including an instruction for players not to celebrate tries "face-to-face".
Among other measures, the use of ice baths is no longer permitted, there can be no face-to-face try celebrations and players cannot eat food together indoors.
Meanwhile, the players involved at Northampton have begun a 10-day isolation period.
"The club has been absolutely rigorous in how we have followed the protocols laid out for us, and despite returning a number of positive tests this week, we were confident we have more than enough of our squad still healthy and available to play the game if required," said Boyd.
"However, we are following the advice we have been given, which was not to play the game and to close our training facility until next week."
Leicester head coach Steve Borthwick said the health of everyone was "paramount" in the current situation.
"We understand the situation, having been through it, and will offer whatever support we can to our friends down the road," he told the Tigers website.
"Our focus will now switch to Bayonne, in the next round of Europe, and maximising our preparation for that fixture."
- Sir Paul McCartney chats to Idris Elba: The music legend reveals his writing process and most-loved songs
- The Cipher: Can you crack it? Thrilling new drama that will keep you gripped