Tottenham's home match against Fulham was postponed on Wednesday after a coronavirus outbreak at the visiting club but the Premier League said it had "full confidence" fixtures could continue despite a nationwide surge in cases.
Fulham returned a number of positive test results on Tuesday and, with a number of players showing symptoms on Wednesday, the Premier League decided to call the match off just three hours before the scheduled 1800 GMT kick-off.
It is the third top-flight game to be wiped out by the virus, following Newcastle's match with Aston Villa earlier this month and Monday's game between Everton and Manchester City.
The decision comes after the Premier League announced on Tuesday there had been a season-high 18 positive tests in its latest round of testing across the competition, already compressed due to the late start to the season.
Britain is struggling with another surge in the virus. More than 71,000 people testing positive for the disease have now died -- one of the worst tolls in the world.
After Manchester City's trip to Everton on Monday was postponed due to a Covid outbreak in Pep Guardiola's squad, all five matches scheduled for Tuesday went ahead.
But Scott Parker's Fulham asked for their game at the Tottenham Hotspur Stadium to be called off, which the Premier League board sanctioned on Wednesday.
The entire Cottagers squad will now be re-tested.
A statement from Tottenham read: "We can confirm that our Premier League home fixture against Fulham, scheduled to take place this evening, has been postponed."
It is understood Spurs are unhappy about the decision and the timing of it. There had been speculation throughout the day that the game might be called off and manager Jose Mourinho indicated his frustration in an Instagram post shortly after 1400 GMT.
Mourinho posted a video on his account of his staff waiting for news with a message which read: "We still don't know if we play. Best league in the world."
The Premier League confirmed the decision to postpone the game was taken following a meeting.
"Fulham lodged a request with the Premier League Board to rearrange the fixture following a significant rise in positive Covid-19 cases, as well as a number of players showing symptoms today," it said in a statement.
"The Premier League board has consulted its medical advisers and the decision to postpone the game has been taken as a precaution and with the health of players and staff as the priority. The group will now be re-tested immediately."
West Brom boss Sam Allardyce voiced support for a "circuit breaker" in the Premier League on Tuesday.
But Manchester United boss Ole Gunnar Solskjaer, whose side beat Wolves to climb to second in the table, called for the competition to continue.
Despite the rising number of cases across the English top-flight, the Premier League said it intended to continue playing.
"With low numbers of positive tests across the overwhelming majority of clubs, the Premier League continues to have full confidence in its Covid-19 protocols and being able to continue to play our fixtures as scheduled," its statement added.
Fulham confirmed the postponement of their match against Spurs followed "a number of the club's players and first-team staff returning positive results from the most recent Covid-19 tests this week".
It added: "This decision follows discussions with the Premier League and advice from Public Health England."
Premier League leaders Liverpool are due to travel to Newcastle for Wednesday's late match.