England midfielder Kalvin Phillips will miss the next two months with a hamstring injury and having just returned to fitness, while Patrick Bamford is also a doubt to face former club Chelsea with the striker back on the treatment table.
It's devastating news for the club's supporters and manager Marcelo Bielsa who may have thought his side were turning a corner.
Struggling Leeds boosted their position in the Premier League table by taking four points from their last two games, following injury-time goals from Brazilian winger Raphinha against Crystal Palace and Bamford against Brentford - on his return from injury.
Now though, the Yorkshire side will be without Phillips in a tough run of games against Chelsea, Man City, Arsenal and Liverpool over the Christmas period.
Initial assessment has shown that Phillips will not be available until February, while Bamford could also be ruled out for the for the next two weeks.
What will annoy Bielsa the most, though, is that the striker picked up his injury in the aftermath of his wild celebration against the Bees, in what was his first appearance since recovering from an ankle injury.
The issue ruled him out for almost three months and saw him miss 11 games across the Premier League and Carabao Cup.
There are other blows for Leeds as club captain Liam Cooper also suffered a hamstring injury in that match and is expected to be out for some time.
With injuries to three key players, Leeds' chances of obtaining any points in their next four look even slimmer than they already where.
Former Aston Villa striker Gabriel Agbonlahor couldn't resist commenting on Leeds' injury situation on the talkSPORT Breakfast.
And while he tipped Leeds to pick up a result when they face out-of-form Arsenal, he says it'll be a brutal run of games for Bielsa's side.
"They're very tough games," said the pundit.
"Those three teams [Chelsea, Man City and Liverpool] are fighting for the title and can't drop points, so they're going to be on form every game.
"So not many points in those games, but the Arsenal game I fancy them to get something… and then the Villa game I fancy them to get nothing."