Cardiff City striker Steven MacLean and midfielder Riccardo Scimeca are set for long injury lay-offs.
MacLean opened his Cardiff account against QPR last month
MacLean has been ruled out for three months after rupturing ankle ligaments in a reserve match on Tuesday.
Scimeca has suffered a set-back to his comeback after pulling up with a problem on the groin that was operated upon over the summer.
Bluebirds manager Dave Jones said he hopes to sign replacements on loan as soon as possible.
"Its a massive blow for both players and the club and I'll have to sit down with the chairman to discuss bringing somebody in," Jones told the South Wales Echo.
"Steve will be out for three months and Riccy has torn a muscle in the same part of the groin.
"He gets to a certain level and it breaks down again, he will see a specialist today [Thursday] and we will know more later."
MacLean joined Cardiff on a free transfer in June, and the 25-year-old has scored once in five appearances so far this season.
Scimeca, 32, was hoping to return to action this month but now looks set for at least another four weeks on the sidelines.