De Bruyne was injured against Inter Milan in the Champions League last month and has missed the English champions' last six fixtures.
City are already without midfielders Rodri and Oscar Bobb due to long-term injuries but Guardiola said he would resist the temptation to call on De Bruyne until the Belgian was comfortable.
"Well, except for Rodri and Oscar, the other ones are in training and getting better, but guys like Kevin for example are not exactly fit," the Spaniard told reporters.
"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 good. He said he doesn't feel good. If you don't feel good, take your time."
Guardiola had a more positive outlook on England midfielder Phil Foden, who last season scored 28 goals for club and country in all competitions and was named PFA Player of the Year but has had a stop-start campaign this time around due to illness.
The 24-year-old was instrumental in City's 2-1 Premier League victory at Wolverhampton Wanderers on Sunday, delivering the corner which led to John Stones' stoppage-time winner.
"He feels much better. The minutes he played last game, for example," Guardiola said.
"With Phil, you realise immediately when he is happy and fit and mentally in the right moment. You realise he's getting better and better."
On Wednesday, City face Czech champions Sparta, who are level with them on four points after beating RB Salzburg 3-0 in their opener and drawing 1-1 with VfB Stuttgart.
"They created a lot of problems (for Stuttgart). I didn't know Sparta until the last two days when I started to watch them and I have a good impression," Guardiola added.