Newcastle United's game at Aston Villa on Friday has been postponed due to a "significant increase" in positive COVID-19 tests at the club, the Premier League outfit said on Tuesday.
"Several Newcastle United players and staff members are now self-isolating at home after returning positive test results in recent days," a club statement said.
"The club's training centre site has been temporarily closed in order to contain the spread of the virus."
Five individuals at the north-east club had tested positive for COVID-19 -- three prior to Newcastle's 2-0 win over Crystal Palace last week and two more over the weekend.
Newcastle lodged a request to have the game postponed and that was approved by the Premier League Board on Tuesday.
It is the first Premier League fixture postponed because of COVID-19 since last season resumed with Project Restart in June.
The club said it was working with Public Health England North East (PHE), local health authorities and the Premier League to identify the source of the outbreak and minimise the threat of further transmission of the virus.
"Newcastle correctly notified PHE regarding a number of positive COVID-19 test results, which is standard practice under Government and Premier League guidelines," the Premier League said in a statement.
"PHE convened a meeting with Newcastle and the Premier League yesterday to assess the situation and advised the club's training ground should remain closed and no group training would be permitted between players until Friday at the earliest."
It said all Newcastle's players and staff would be tested again this week.
"The Premier League wishes those with COVID-19 a safe and speedy recovery and will rearrange the postponed fixture against Aston Villa in due course," it said.
This weekend will see the return of a limited number of fans to some Premier League games for the first time since the pandemic took a grip on the country in March.
Clubs located in the government's Tier 2 regions, including London and Merseyside, can have 2,000 fans in attendance.
Fans return to English grounds, but told not to celebrate goals too much
Fans will return to English Football League grounds on Wednesday with several clubs opening their doors to limited numbers, but the match-day experience will be far from what they are used to.
They will be greeted by one-way systems, temperature checks, strict entry times and minimal catering facilities while goal celebrations must be restrained.
Championship (second tier) clubs Luton Town and Wycombe Wanderers will signal the end of England's national lockdown as they host Norwich City and Stoke City respectively.
Apart from a few pilot test events at some EFL fixtures in September, allowing 1,000 fans, England's soccer stadiums have sat silent since the COVID-19 pandemic took hold in March.
Luton and Wycombe are both in Tier 2 areas of the country, which under government guidelines means attendances of up to 2,000 are allowed at outdoor sporting events.
While it is a step towards sporting normality, the old routine of meeting with a bunch of mates for a pint and meal, then dashing into the ground five minutes before kickoff will be impossible under strict guidelines.
Luton have limited their attendance to 1,000 'ambassadors' selected from season ticket holders of at least 10 years.
"As with everything in our daily lives during 2020, all Hatters should understand that the matchday experience will be very different to what you are used to pre-Covid," the club said in a message to fans.
Seats will be allocated by the club to ensure social distancing; health questionnaires and temperature checks must be completed and fans must adhere to selected arrival times.
Face coverings will be mandatory while at the final whistle, fans will exit one row at a time.
Wycombe will limit their attendance to 1,000 as they test out new measures to ensure a safe return for fans, although like Luton they hope to move to 2,000 for their next home game.
One-way systems will be in place around the stadium and while moving to and from their seats, fans must do so "back to back" from other supporters.
"Avoid hugs, high fives, handshakes, or other close contact with people who are not in your social bubble, take care when singing, chanting, or celebrating," a code of conduct instructs fans on Wycombe's website.
Supporters have even been told not to touch the ball if it is kicked into the stands.
League One club Charlton Athletic can accommodate 2,000 fans for Wednesday's home game against MK Dons and while no catering will be available, a "free hot chocolate" will be offered as a welcome-back gesture.
Shrewsbury Town, who like Charlton staged a pilot test event in September, will have 2,000 fans at their Montgomery Waters Meadow ground for Wednesday's game with Accrington Stanley.
In League Two Carlisle United will allow up to 2,000 fans for their game against Salford, as will Cambridge United as they host Mansfield Town.
Arsenal will be the first Premier League club to have fans for a competitive fixture since March when they host Rapid Vienna in the Europa League on Thursday.