Chelsea midfielder Frank Lampard and Manchester United's Shinji Kagawa are both major doubts for the summit meeting between the Premier League's top two at Stamford Bridge on Sunday.
Lampard was replaced after 17 minutes during The Blues' Champions League defeat to Shakhtar Donetsk with a reoccurrence of a calf injury, while Kagawa was taken off at half time in United's win over Sporting Braga with a knee problem.
The pair are set to square off this weekend, with the aim of laying down a marker ahead of what is expected to be a three-pronged race for the title along with champions Manchester City, but both sides could have crucial components of their season absent.
"It's basically a recurrence of an old injury," Chelsea boss Roberto di Matteo said.
"He was training with us fine and there were no alarm bells before the game. He was in good condition to play."
"We thought it was the right choice to put on Hazard but we were too individualistic in our pressing in the first half, and too stretched as a team which conceded space to Shakhtar."
Lampard has made just four league starts for Chelsea this season, with the likes of Oscar, Ramires and John Obi Mikel often preferred in the centre of midfield with his indispensable status at Stamford Bridge damaged as a result.
Meanwhile, Kagawa, who moved to United from Bundesliga champions Borussia Dortmund in the summer, picked up a knee injury mid-week through the first half of the Champions League group win against Braga but was only withdrawn at the interval.
The 23 year old has started in six of United's league games this season and has impressed in the early stages of his Old Trafford passing with his neat passing and link up play particularly with fellow new addition Robin van Persie.
But the Japan international could now be absent for one of United's biggest games of the campaign at Chelsea this weekend, with a scan set to reveal the full extent of the damage.
"Shinji twisted his knee," Sir Alex Ferguson said. "We had to take him off. He struggled on for 20 minutes after he got the injury. We'll assess it in the morning as it's too early to say what the damage is."