The Tigers meet the Belgian side in the first leg at Daknamstadion, and the former Manchester United defender will make sweeping alterations to the side that beat Queens Park Rangers 1-0 on Saturday afternoon.
Bruce doesn't see the changes as taking the competition any less seriously than his team's Premier League campaign.
On the contrary, he believes that he will be giving his players who fired them into Europe a reward for their hard work of last season.
Bruce also believes that the trip will be a stern test of his charges' capabilities and cited Belgium's ever-increasing reputation as one of the primary reasons for why he thinks the game against Lokeren will be a tricky tie.
He told the club's official website: “Lokeren are a very, very good side from what I’ve seen of them and as we know, Belgium is producing some very good players.
“It will be a difficult game for us. As I’ve said, I’ll be changing my team around and giving the players who got us into Europe the chance to play in Europe.
“I think working it that way is what gives us the spirit that we’re playing with. They’re all going to get their chance. I had to leave people off the bench at QPR on Saturday, George Boyd in particular, who have done wonders for me.”
Tom Ince, Robert Snodgrass, Jake Livermore and Andy Robertson all made their Hull City debuts on Saturday against QPR, but with a visit from Stoke City up next in the Premier League, Bruce is expected to recall some of his fringe players.
Livermore arrived for a reported fee of around £8 million earlier this summer, while Snodgrass was brought to the club from Norwich City for £7 million.
Harry Maguire and Robertson arrived for a combined fee of around £5.5 million and Tigers chairman Assem Allam has certainly backed Bruce in the transfer market in 2014.
Back in January, they spent around £14 million on the signings of Nikica Jelavic and Shane Long, but the Irishman has since moved to Southampton for £12 million.