Having secured a first Premier League win of the season against Norwich, the Tigers boss named a completely different starting line-up at Leyton Orient.
Few squad players managed to boost their chances of a regular starting berth in east London, where substitute Robbie Brady's extra-time strike earned the visitors a scarcely-deserved 1-0 win.
City will find out their third-round opponents later on Wednesday and Bruce suggested he will again make sweeping changes in that tie.
"You don't want to undermine it, of course you don't," the Hull boss said.
"You want to give your squad a chance because the difficulty of playing in the Premier League is that it makes this the ideal opportunity to play the squad.
"They've played this evening but we all know the Premier League has got to be the priority.
"We are new in there and we've got to make sure we do everything we possibly can to stay up, keep the squad intact.
"The more games you play, the more chance you have of getting an injury to your big players and that is always in the back of your mind.
"We're delighted we got there, but it wasn't a great performance. Orient played very well on the night."