Bruce made a full 11 changes for the second-round success over Leyton Orient - though he did need Robbie Brady to come from the bench to score the winning goal - and is ready to make widespread alterations again when Huddersfield visit the KC Stadium.
Survival in the Barclays Premier League is the overarching aim of the Tigers' season and a third-round clash against the Terriers is not likely to deflect Bruce's focus.
He has ready-made stand-ins in several positions, with Steve Harper on hand to relieve Allan McGregor in goal, Alex Bruce and Abdoulaye Faye trusted to take over at centre-half and out-of-favour strikers Matty Fryatt and Nick Proschwitz available to reprise their forward pairing from the Orient game.
The side are less well stocked on the flanks and in central midfield, though first-teamers Stephen Quinn and David Meyler may appreciate additional game time having spent more time on the bench than the pitch thus far.
Asked after Saturday's impressive 3-2 success at Newcastle if he would make alterations to his winning team, Bruce said: "Yes, many.
"We're not going to be disrespectful to the competition but we made a lot (of changes) last time and we'll certainly do that again."
Tom Huddlestone, a club-record signing from Tottenham in the summer, has been in fine form in recent games and is one of those likely to be handed a rest.
He had rather too many weeks on the sidelines in his last couple of seasons at Spurs but accepts Bruce's selection policy is not going to change for Huddersfield.
"First and foremost, we have got to try to sustain Premier League status for next season, but if you can have a good cup run as well, it bodes well," said Huddlestone.
"The manager has got a fairly deep squad as well - the last round in the cup, he changed 11 players and they got the right result, so he is fully within his rights to do that again, I guess."
Bruce's conviction that his top performers should not be risked will only have increased in the closing moments of the Newcastle match when James Chester suffered a hamstring injury.
He will now join club captain Robert Koren (broken foot) on the sidelines, while Paul McShane and Maynor Figueroa are also short of full fitness.
"The down side for us is that we've lost another one in James Chester," said Bruce.
"It's a big loss to us and it's one thing we can't afford. Two or three are missing now and we hope that's as much as it gets.
"Ches did his hamstring. He stretched in the last minute trying to make a block but unfortunately his hamstring popped and he'll be out a long time I'd have thought.
"I don't think it's just a grade one tear the way he held it. He's probably out for four to six weeks."
- Sports & Recreation
- Barclays Premier League
- Alex Bruce
- Leyton Orient