Sheffield United midfielder John Fleck will miss between four and six weeks with a back injury.
The Scotland international could also miss their crucial European Championship play-off match against Serbia in Belgrade on November 12, as well as the Nations League game away to Slovakia three days later and the trip to Israel in the same competition on November 18.
Fleck’s problem is the latest in a growing list of injury concerns for the Blades.
Defender Jack O’Connell is likely to miss the remainder of the campaign after undergoing knee surgery, while striker Lys Mousset has yet to play this season as he recovers from a toe injury.
Forward Oliver Burke was only fit enough for the bench in Sunday’s 1-1 draw with Fulham at Bramall Lane due to a knock and left-back Max Lowe’s Premier League debut was cut short on after he suffered a concussion after just 20 minutes.
Blades’ boss Chris Wilder said: “John was down to play, it’s another unfortunate injury. He suffered one of those injuries you don’t get 99 times out of 100.
“Speaking to the medical people, how unfortunate he was to land on such a small place on his back to do the damage that he has done is so unlucky.
“It will be four to six weeks and it’s another blow that we have to take on the chin.”
On Lowe’s knock to the head, Wilder added: “He’s got concussion, he took a nasty whack and got blurred vision, which is desperately unfortunate for us following on from Fleck, Mousset and O’Connell.
“We are being tested a little bit and can do without that. Max has been fabulous.”
The point earned against Fulham was the Blades’ first in the Premier League this season and their task does not get any easier in the coming weeks.
United face Liverpool at Anfield on Saturday evening,with the visit of Manchester City on October 31 then followed by a trip to Chelsea the following week.