Hull duo Andy Dawson and Stephen Hunt are unlikely to be fit for the crunch clash against Fulham at the KC Stadium.
Stand-in captain Dawson limped off with a hamstring injury during last week's 3-2 defeat at Portsmouth and leading scorer Hunt has been sidelined for more than a month with a foot problem.
Manager Iain Dowie, who takes charge of his first home game, will have George Boateng back from suspension while Jozy Altidore has recovered from a hamstring injury but youngster Liam Cooper (ankle) and Amr Zaki (knee) are set to miss out.
Club captain Ian Ashbee (knee) participated in training for the first time this week after almost a year on the sidelines but remains some way away from a first-team return.
Kamil Zayatte (knee) and Anthony Gardner (ankle) are also long-term injury victims.
Dowie remains hopeful Gardner will return before the end of the season but admits Zayatte may not.
Dowie has told his Hull players to take the positives from last week's Portsmouth heartbreak into the crunch Premier League clash against Fulham.
Hull return to the KC Stadium looking to end a run of five successive defeats but, at the end of his first week in the north-east, Dowie insists it is far from all doom and gloom.
He said: "I watched the video a few times and it doesn't get any easier but we've got enough good characters around the place that came in bright and bubbly and we've had a good week. The response has been good, there's a focus about them. I've learned they're a group of lads that really care about the club.
"Sometimes in your darkest moments, you find something within yourself. That's the time when inspiration comes to you. We have to work alongside each other and hopefully each player on Saturday will be an inspiration for the one alongside him.
"The key is to use what's been a positive start in lots of creative ways as a strength. It's very important we start the game in a positive frame of mind."
Fulham boss Roy Hodgson will need to check on Bobby Zamora's stomach problems ahead of the clash.
Zamora was substituted during the FA Cup defeat at Tottenham in midweek after suffering severe cramps during the half-time interval.
Andrew Johnson and John Pantsil remain in the treatment room while David Elm has been ill.
Fulham skipper Danny Murphy has told his team-mates not to forget their Barclays Premier League duties as they go in search of silverware.
Hodgson's men are still in the Europa League and expectations have risen following their famous victory over Juventus to earn a place in the last eight.
They face German side Wolfsburg on Thursday but Murphy is focused on the trip to Hull at the weekend and he believes Hodgson's squad is capable of coping with the demands of extra fixtures.
"Regardless of what is going on in other competitions, we still want to kick on and maintain our top-half placing," Murphy said.
"All through the season I've talked about our character and strength and every member of the squad deserves credit because over the past eight months everyone has played their part.
"When you look at the difference between now and last season, when we played a similar team for the majority of it, it shows how much the squad has developed. I think it has made us a stronger club."
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