Sheffield United quartet Harry Maguire, Jamie Murphy, John Brayford and Stephen McGinn are all doubtful for the FA Cup quarter-final clash with Charlton.
Defender Maguire has missed the last two games due to a knee injury, while Murphy and Brayford sat out the midweek win against Peterborough with respective groin and calf problems.
McGinn, meanwhile, suffered a recurrence of a back injury in midweek.
Terry Kennedy, who made his full debut against Peterborough, could continue in central defence if Maguire is ruled out, while on-loan Ben Davies stepped in for Brayford.
Manager Nigel Clough does not think his side are favourites.
The Blades, who aim to become the first third-tier side to reach the last four of the famous competition since Wycombe in 2001, have ousted Aston Villa, Fulham and Nottingham Forest in the last three rounds.
They now welcome the Sky Bet Championship strugglers, who beat United's city rivals Wednesday to book their spot in the last eight and deny the chance of a Sheffield derby.
The Blades are on an impressive run of form having won their last eight games in all competitions, conceding only one goal along the way. Clough is keen to play down his side's chances, though admitted not playing the Owls could be an advantage.
"I would disagree that we are favourites, when you are playing a team from the division above then that takes precedent as to who are favourites or not," the former Derby boss said.
"I know we are at home and have won a lot of games but I still think their Championship status makes them favourites.
"An FA Cup quarter-final, the motivation shouldn't be less, whoever we are playing, there is a semi-final at Wembley at stake whether we were playing Charlton or Sheffield Wednesday.
"I think not playing Wednesday means we are concentrating on the football, it's just an FA Cup quarter-final now, rather than a Sheffield derby."
Charlton are hopeful Michael Morrison, Jordan Cousins and Simon Church will be fit.
Defender Morrison suffered a thigh strain during last weekend's 3-0 Sky Bet Championship defeat by Leicester while midfielder Cousins and striker Church also picked up knocks, with the latter forced to withdraw from the Wales squad in midweek.
Full-back Chris Solly and centre-half Leon Cort remain sidelined by knee injuries although both are making progress.
Fit-again goalkeeper Ben Hamer (ankle) is set to keep his place ahead of January signing Yohann Thuram-Ulien.
Chris Powell wants to put an end to the jokes about Charlton and the FA Cup.
The Addicks have a laughable modern-day record in the competition but are now on the verge of a first semi-final since 1947, the year of their one and only triumph.
And it they can get past United, Charlton will be back at Wembley for the first time since their epic 4-4 play-off final and penalty shoot-out win over Sunderland in 1998.
"It's a competition I always feel is one we traditionally don't do well in," said Valley boss Powell.
"It's a bit of a standing joke, Charlton and the cups, but we have turned that around somewhat, which is pleasing.
"It's certainly captured the imagination of our supporters, which is the number one priority for me.
"Of course we still have a big game to negotiate but I'm determined to get us to the new Wembley as we haven't been there yet.
"We were at the old one in 1998 and everyone knows what happened for us that year, so it would be wonderful to get to Wembley again and have 30,000 red and white fans there."