The Belgian missed Manchester City’s midweek FA Cup win over Sheffield Wednesday after picking up an injury in the closing stages of the Carabao Cup final.
De Bruyne has told Guardiola he feels better and the Catalan expects him to improve before the derby, but says it is too early to know whether the midfielder will be fit enough to be involved at Old Trafford.
"He is getting better," he said. "Today we didn’t train and tomorrow he will improve.
"This morning he was with the physio and he said he feels better. Not perfect, but he feels better. We will see."
There are similar doubts in the United camp after Ole Gunnar Solskjaer confirmed it is ‘touch and go’ as to whether Harry Maguire will recover from an ankle injury, while question marks also remain over Aaron Wan-Bissaka and Daniel James.
One player certain to miss out for City, however, is Leroy Sane.
The German winger returned to action with our Elite Development Squad (EDS) last week, but Guardiola admitted he is still weeks away from being ready to play for the first team.
"He is making big progress but still he’s not 100% fit," the boss explained.
"He has to be ready and fit to play official games right now. Maybe that will be good [more EDS games]. I think weeks and games will be good.
"He will feel it first himself because every week he is getting better and after I will try to give him minutes to get back as soon as possible.
"But, for this game, no.”
With Guardiola conceding City are fighting for second place in the Premier League and United aiming to secure Champions League football, he acknowledged the 182nd Manchester derby will have a slightly different feel to it.
However, the Catalan believes the trip to Old Trafford is an opportunity to build on our recent good form and improve further.
Victory, he says, is the best way to do just that ahead of an important run of matches.
"It’s always special," he added when asked about the derby atmosphere.
"The situation this season is a little bit different because we are playing to improve and finish second, not to win the title. For them it is so important to qualify for Champions League.
"But it is special to improve, to prepare for the next game. Especially two knockout games at the end of the month against Madrid and Newcastle and to improve what we want to do.
"In Sheffield there were moments when we weren’t perfect, that’s why we struggled to attack more fluently. The moment we did it, we attacked better.
"Every game is a chance to improve. That’s nice. To do it against United, a big team in a derby, is the best way to improve."