Roger Federer has already pulled out of next month's Australian Open, while Novak Djokovic awaits a decision on whether he'll be allowed to compete with his current vaccination status.
Rafael Nadal is set to take part but with the 35-year-old Spaniard coming back from a foot injury as well as COVID-19, his participation isn't guaranteed.
Therefore, it's a very real possibility that the none of the prestiged 'Big Three', who share 60 Grand Slam titles between them, will compete in the first major of 2022.
It's a scenario that Nick Kyrgios coined "a disaster" earlier this week, stating that the absence of all three stars would tarnish the reputation of the sport.
However, current world No. 4 Stefanos Tsitsipas has taken a different view, suggesting their absence would allow fans to see the next generation of the sport's stars.
"That is how it's going to be generally in a few years time, potentially three years time," he said during a press conference on Thursday.
"So getting used to it early, it's pretty much the new reality. Let's see how tennis works out without the top three - I really want to see which players are going to prevail."
It's certainly an optimistic spin on a worrying situation, but with eight of the world's top 10 under the age of 25, perhaps the Greek star has a point.
The only two exceptions in the top 10 are Nadal and Djokovic, and Tsitsipas believes that them being removed from the equation will show how the younger players have "something different to offer".
"We are able to bring tennis to a very high level - we have something different to offer than what Djokovic or Federer or Nadal have," Tsitsipas said.
"It's not our responsibility, we just have to work hard every single day, bring the best out of this game and set the bar high. "I'm playing for myself and if young kids are inspired by what we do then we've done our job right."
Tsitsipas starts his season at the ATP Cup in Sydney where he will be the third-highest ranked player in the tournament after Daniil Medvedev and Alexander Zverev.
Greece has been drawn in the same group as Georgia, Poland and Argentina. They will play their first tie on Saturday against Poland with Tsitsipas set to take on Wimbledon semi-finalist Hubert Hurkacz.