Curtis Davies and captain Matt Oakley will miss the fourth-round tie against Midlands rivals West Brom.
Defender Davies limped off with a hamstring strain midway through the second half of the Championship defeat at Swansea on Saturday.
It is hoped the centre-half, on loan from Aston Villa, will not be out for long and he could even come back into the reckoning for the league visit of Preston at the weekend.
Oakley, however, could be set for a month on the sidelines after the midfielder suffered a thigh strain against the Swans.
Michael Morrison is likely to replace Davies while Julio Moreno, Yuki Abe and Paul Gallacher, should he recover from the back problem that ruled him out of the trip to south Wales, are Sven-Goran Eriksson's options to replace Oakley.
West Brom are set to be without central defender Jonas Olsson and striker Marc-Antoine Fortune.
Olsson had to be substituted after 55 minutes of Saturday's 2-1 home win over Fulham with an Achilles problem.
Fortune was taken off at the same juncture with an ankle injury after scoring his first goal of the campaign.
Pablo Ibanez and Roman Bednar could deputise for the injured duo after replacing them against the Cottagers.
Four-goal leading scorer Peter Odemwingie, who has missed the last two games with a knee setback, will also not be involved at the Walkers Stadium.
Baggies head coach Roberto Di Matteo is likely to again rotate his squad.
Albion (from): Carson, Jara, Tamas, Shorey, Scharner, Mulumbu, Brunt, Morrison, Thomas, Pablo, Bednar, Tchoyi, Cox, Dorrans, Myhill, Reid, Moore, Mantom, Barnes, Cech.