Mannone, on loan from Arsenal, has sustained a thigh injury similar to the one that sidelined him throughout January and February, so another loanee, Aston Villa's Brad Guzan, will return to the starting line-up.
Manager Nigel Pearson is hoping Mannone recovers his fitness before Guzan's loan spell expires after the clash at Watford on April 9.
Defender Liam Rosenior has missed training this week due to a foot injury sustained in last weekend's win at Nottingham Forest, but is expected to recover in time.
Recent loan signing from Liverpool, winger David Amoo, is hoping to make his first start for the Tigers, while Tijani Belaid, Jack Hobbs, Tom Cairney and Richard Garcia are all pushing for first-team recalls.
Pearson has no other new injury or suspension problems as his side look to make up ground on the top six after two defeats in their last three games.