The Cleveland Browns will try to secure a play-offs spot without six players, because of a positive COVID-19 test and subsequent contact tracing.
Cleveland's game against the New York Jets will be played as scheduled on Sunday, an NFL spokesman said, despite the Browns having to close their practice facilty as a precaution.
The stunning news for the Browns (10-4) came as they were preparing to fly to the New York area - the flight was delayed more than four hours - and potentially lock up a first post-season berth since 2002, the league's longest drought.
Starting linebacker B.J. Goodson was the first to be placed on the COVID-19 list after he tested positive.
Then, after the team completed contact tracing, Jarvis Landry and fellow receivers Rashard Higgins, Donovan Peoples-Jones and KhaDarel Hodge were also placed on the list, knocking them out of the game.
Rookie linebacker Jacob Phillips, who may have started for Goodson, is also out.
Per league rules, Goodson will miss Sunday's game and the January 3 match-up against the Pittsburgh Steelers is also in question.
The league says any player testing positive has to stay out at least 10 days before being eligible to return.
For Landry, this will be the first game he has missed in seven seasons - after playing 110 games in a row.
"ANNOYED," he posted on Twitter.
Higgins, too, expressed his disappointment, writing: "I don't even have covid!!!"
Like numerous NFL teams, the Browns have been dealing with positive cases for most of the season.
Defensive star Myles Garrett missed two games after contracting the virus.
In the NBA, the Houston Rockets will be without DeMarcus Cousins, Eric Gordon, Mason Jones and John Wall for at least two games while they complete quarantine.
The quartet's quarantine period will end Wednesday provided they test negative.
The Rockets face the Portland Trail Blazers on Saturday in their season opener after their game against the Oklahoma City Thunder on Wednesday had to be postponed because Houston did not have enough available players.
Houston All-Star James Harden is expected to play against the Trail Blazersafter he served a four-day quarantine for breaking protocols - for which he was fined $50,000 ($A66,000).
Meanwhile, Arsenal said defender Gabriel was self-isolating because he had close contact with someone with COVID-19 and will miss the Premier League club's next three matches.