Captain Robert Koren has the most serious problem, with a fractured bone in his right foot keeping him out of action for anything up to two months.
Left-back Maynor Figueroa, ever present thus far, is suffering from a groin complaint but has also been granted compassionate leave to attend to a family problem in Honduras, while his likely deputy Paul McShane is out with a hamstring injury.
Bruce also has a slight doubt over Robbie Brady, though the Republic of Ireland international is confident of playing through the pain of a strained stomach muscle.
"The one thing you need is a little bit of luck where these things are concerned and we've lost at least a couple this week," said Bruce.
"Robert is the main one, we expect him to out for six to eight weeks and that's a big loss. Then there's McShane and Figueroa...though we don't expect them to be out for more than a week or 10 days.
"All of a sudden from everyone being okay a week ago we have got two or three struggling."
Liam Rosenior, who was pulled from a midweek reserve team fixture, looks most likely to benefit by providing cover on the left of defence, while Bruce can also call on summer signing Yannick Sagbo again following a three-match suspension.
The Ivorian striker was dismissed for aiming a headbutt at Norwich's Russell Martin on his home debut, and now has a point to prove to his new club.
"He let himself down more than anything. His first home game in the Premier League and he gets sent off after 20-odd minutes; you don't have to be a rocket scientist to say he's let himself down," said Bruce, who has a straight choice between Sagbo and the mis-firing Sunderland loannee Danny Graham.
"Everyone else we've brought in has settled in and done quite well in their new surroundings and he's the other side of that.
"But what's done is done. We all make mistakes, he's been punished and I don't think he'll do it again.
"I've got a decision now whether to bring him back in."
Bruce, Northumberland born and a lifelong Newcastle supporter, knows all about the intensity of St James' Park and believes a trip to the north east completes one of the most challenging periods imaginable for a newly-promoted side.
Hull's first two away matches were at title challengers Chelsea and Manchester City and they failed to spring a surprise in either encounter.
Nevertheless, Bruce believes his players are up to the task.
"We knew the first few weeks away were going to be pretty special - Chelsea, Manchester City, Newcastle...but that's the Premier League," he said.
"The squad are still looking forward to the challenge. We've proved so far that we can play at this level but we have to be at our best to do that.
"If Newcastle get a head of steam it's a very passionate place to play football and we have to handle that atmosphere."
- Sports & Recreation
- Robert Koren
- Maynor Figueroa
- David Meyler