Leeds midfielder Kalvin Phillips has been ruled out for two months with a hamstring injury, while striker Patrick Bamford has also suffered a setback on his return from an ankle problem.
Both players were hurt in Sunday's 2-2 with Brentford, with Bamford appearing to injure his own hamstring in celebrating his stoppage time equaliser at Elland Road.
While the striker faces around two weeks on the sidelines, Phillips is expected to be out for far longer after he pulled up shortly after half-time against the Bees and headed straight down the tunnel.
Centre-back Liam Cooper also hurt his hamstring in the same match, although the timeframe of his absence is unclear at this stage.
The England international only recently missed two games with a calf problem - both of which the Whites failed to win. Meanwhile, Bamford and defender Luke Ayling only returned at the weekend having been out since mid-September with ankle and knee injuries respectively.
German centre-back Robin Koch is a longer-term absentee for Marcelo Bielsa's side and is yet to feature at all this season.
Those defensive injuries mean that Phillips has deputised in central defence at times this season, but Bielsa will now need to find cover for him in midfield. Adam Forshaw's own recovery from a long-term injury and subsequent encouraging form should help.
Speaking to 90min earlier in December, Phillips revealed he had almost missed Euro 2020 with a dislocated shoulder.
"That's supposed to be a 3-4 week injury and I had to somehow get fit enough for the first game, which the fitness staff at Leeds and England made possible," he said.
"It's probably the worst feeling I've ever felt, I had to drive all the way to Harrogate an hour away, just sat in the back of the car with my shoulder dislocated."