The Tigers won praise for their wholehearted performance against Manchester United on Boxing Day, taking a 2-0 lead inside just 13 minutes before eventually being reeled in as the champions ran out 3-2 winners.
And if the result was hard to take, the physical effect on Bruce's squad simply rubbed salt into the wounds.
Goalkeeper Allan McGregor, who collided with Ashley Young early on and never fully recovered, and in-form midfielder David Meyler both came off with knee injuries at half-time against United and appear to have no chance of taking part in Saturday's home clash with Fulham.
Alex Bruce finished the game but was not fully fit by the final whistle, while a number of other players carried on with knocks.
Having not won in five Barclays Premier League outings, Hull boss Bruce sees the visit of relegation battlers Fulham as a key fixture but could be forced to ring the changes.
"Both McGregor and Meyler have knee injuries," said Bruce.
"Meyler is a concern because it is the same knee he's injured before when he was out for a long time.
"McGregor's came from a challenge by Ashley Young that went unpunished. It looked late to me.
"He's got a nasty one. They'll both have X-rays and scans.
"Alex has a calf problem and there were one or two others with knocks at 90 minutes too.
"But we have to go again with this ridiculous schedule we have to play.
"Two games in 48 hours...it's ridiculous when we have so much at stake, but we have to recover and be ready for Fulham."
Hull have been one of the division's surprise packages so far this term, outperforming their fellow promoted sides Crystal Palace and Cardiff and reaching Bruce's target of 20 points by Christmas Day.
But with several of the sides beneath them winning in recent days, victory over Rene Meulensteen's Cottagers has suddenly become desperately important to maintain a comfortable buffer over the relegation places.
The confident performance against David Moyes' Red Devils should give them reason for cheer but Bruce has warned the game will follow a completely different pattern.
"After Boxing Day and Manchester United coming to town it's after the Lord Mayor's show, that's always a worry," said Bruce.
"It's back to Fulham and that's arguably the bigger game for us. We must have the mental capacity to play two games so quickly and get something from the second game.
"We need to pick up some points from the teams down below us. It's alright getting plaudits for playing well against teams like Manchester United, Chelsea, Manchester City but we have to perform on Saturday.
"When the big teams come here the expectation is that they will come and beat us, but I don't think Fulham will be playing four up front like United did at the end. We'll have to find another way to get something."
He added: "We need to make sure the gap we have stays that way. We're ahead of the relegation areas and the challenge is to maintain that over the coming months.
"If we can beat Fulham it will make a hell of a difference."