We face the Czech side for the first time at the Etihad Stadium at 20:00 (UK) aiming to maintain our position in the top eight sides that automatically qualify for the Round of 16.
De Bruyne has been out for since being forced off with a groin injury in our last Champions League clash at the Etihad against Inter, just over a month ago.
The Belgian missed five months of last season after surgery and Guardiola said he will not rush him back and wants him to feel comfortable.
“Well, except for Rodri and Oscar, the other ones are in training and getting better, but guys like Kevin for example not exactly fit,” the City boss said in his prematch news conference.
“It’s not a new issue but he doesn’t feel completely fine. Kevin is not 22 years old he has to be fit for his football.
“He doesn’t feel comfortable that he can express his incredible potential at his best.
“He is training better but he doesn’t feel. He said he doesn’t feel good. If you don’t feel good, take your time.”
Walker was not fully fit for Sunday’s Premier League clash with Wolves that we won with a dramatic injury time goal from John Stones.
And Guardiola said he picked up a knee injury while away on international duty with England.
“I think he is not ready,” he said. “Since being with the national team he’s not been well.”
Nathan Ake was back on the bench against Wolves after being sidelined since sustaining a hamstring injury in September whilst on international duty with the Netherlands.
And Guardiola was full of praise after the game for Phil Foden’s pinpoint corner that led to our late winner and says he is returning to his best.
“He feels much better, the minutes he played in the last game for example,” the Catalan added.
“Phil you realise immediately when he is happy and fit and mentally in the right moment you realise he’s getting better and better.”