The Montreal Canadiens and Philadelphia Flyers were to play in an empty Bell Centre on Thursday night due to a "spiraling rise" of COVID-19 cases.
The Canadiens announced about two hours before puck drop that Quebec public health officials had requested that no fans attend the game.
"We have accepted this request in order to help ensure the safety and security of our fans and fellow citizens throughout our community," the Canadiens said in a statement.
There's been no indication that the rest of the Canadian provinces will follow Quebec's lead, a source told ESPN's Greg Wyshynski, but the league expects there will be ongoing conversations about it in light of Thursday's decision.
The Canadiens said there will be an update on the status of Saturday night's game against the Boston Bruins, who currently have a six players in COVID-19 protocol, including captain Patrice Bergeron and star winger Brad Marchand.
The Canadiens said they have been assured they will be allowed to return to partial capacity at the Bell Centre beginning in January.
Fans who had tickets are being refunded, with credits going to season ticket holders.
Earlier this week, Ontario capped capacity for Toronto Maple Leafs and Ottawa Senators games at 50%.
More than 140 NHL players have been on the protocol list this season in a league that has proudly noted that all but one of its approximately 700 players are considered fully vaccinated, even if booster shots are not mandated.
It is a discouraging trend for the league, which plans to allow its players to participate in the Winter Olympics in China in February unless COVID-19 disruptions prove to be too much.
The Associated Press contributed to this report.