The Belgian has made just one substitute appearance this season after suffering a knee injury in training on August 15.
Guardiola decided not to risk De Bruyne, 27, for the game against Liverpool before the global break but has confirmed he will be in the squad to face Burnley, although he may not play a full 90 minutes.
As well as manager Jose Mourinho, Paul Pogba has come in for sustained criticism over his efforts and some of the players at Old Trafford are starting to resent the treatment.
'Of course, there's no doubt how important he is for us'.
He said: "Manchester City has been a huge part of my life and my career and I'm immensely proud of what I and my team-mates achieved in that period".More news: Unai Emery refuses to get carried away by Arsenal's great run
Sancho, 18, left City for Borussia Dortmund last summer in search of game time and has registered more assists than any other player in Europe this season.
Guardiola decided against rushing City's player of the year back for that top-of-the-table clash.
"Luke reacted in the best possible way in these hard moments, the moments where he was not selected, not playing regular, he was saying the same all the time, "I want to play for you and United I am going to make it and be the player you want me to be". They also think that they are the targets because the pundits do not want to go for Mourinho, and face his wrath. I hope the situation is retrievable.
"There have been some incredible goalkeeping legends throughout Manchester City's history, and I feel privileged that the club has chosen to recognise me amongst that number". But Guardiola says he is not concerned about interest from German clubs despite the early success of Sancho. "That doesn't count but you have to take it", he added.
"He did it, he faced the process in a courageous way he started the season before the season start in the best possible way where he went for holidays with a club fitness coach and he arrived in day one in much better conditions than a player that has a holiday just for fun and rest. I'm glad he's playing well".