Dieter Hecking's side saw their bid to reel in leaders Bayern Munich dented with a 1-0 defeat to Augsburg on Saturday - Wolfsburg's seventh game in 21 days and their fourth successive away game.
It leaves Hecking's men 11 points off Bayern, with the DFB-Pokal and the Europa League their only realistic chances of silverware this term.
A 2-0 aggregate win over Sporting in the previous round ensured progression to the last 16, with Wolfsburg boasting three consecutive continental clean sheets.
While De Bruyne thinks tiredness was a factor on Saturday, he urged his team-mates to wake up and impress against Roberto Mancini's side at Volkswagen Arena in the first leg of their last 16 tie.
"You're on the go the whole time, you never get to relax and you also don't get enough sleep. That's something we really felt [on Saturday]," De Bruyne told the club's official website.
"But we were under the same strain last week and we managed to deal with that.
"It was our wish to play so many games, so we are not going to start using tiredness as an excuse."
Inter booked their place in the second knockout round thanks to a 4-3 win over Celtic, with the progression marking another step forward for Mancini after his return to the club in November.
Mancini has seen his side lose just once in their last seven games going into their first leg with Wolfsburg, a run that includes battling from two goals down to draw 2-2 at Napoli at the weekend.
As Inter bid to maintain their unbeaten streak in this season's Europa League, Mancini told Gazzetta TV: "When I came in, the squad was low on morale because of some negative results.
"But I found a very willing group of players and they've improved extremely quickly. You don't often get a group capable of making such progress, and it certainly wasn't easy to change things with the season in full flow.
"Can we improve at the back? We're working on it - it's not easy to switch to a back four after such a long time playing with a different system.
"In any case, it's wrong to always blame the defenders. Defending is the job of the entire team and my hope is that the lads all improve as one."
Mancini will likely be without Yuto Nagatomo (thigh), while Aaron Hunt (knee) is doubtful for Wolfsburg.
