Man City's treble bid hit by De Bruyne injury blow
De Bruyne has been left out of Belgium's squad for their forthcoming friendlies against the Republic of Ireland and England because of a groin strain.
Belgium coach Domenico Tedesco claimed De Bruyne has been struggling with the problem for the "last few matches".
City boss Guardiola said the 32-year-old felt the injury before he was substituted in the second half of last weekend's 1-1 draw at Liverpool in the Premier League.
De Bruyne had already missed a large chunk of the season after aggravating a hamstring injury in City's league opener at Burnley in August.
He will be sidelined for Newcastle's visit to the Etihad Stadium and Guardiola could not confirm if he would be available for the crucial showdown with Premier League leaders Arsenal on March 31.
"He already played in Anfield with some problems. But he is getting better. He is not ready for tomorrow," Guardiola told reporters on Friday.
"We spoke with the manager of Belgium and he decided. That's why I'm grateful because he didn't feel good. Hopefully now he can recover for the last part of the season.
"All the players today in modern football, they are not clean (healthy). Always they have problems. The day after the game he didn't feel good, so it's better to take a step back."
De Bruyne is not Guardiola's only injury concern as Brazil goalkeeper Ederson will also miss the Newcastle game.
Ederson came off against Liverpool with a muscle injury and Stefan Ortega will deputise against Newcastle.
Guardiola is hopeful Ederson can recover to face Arsenal, who sit one point ahead of third placed City in a gripping title race.
"Ederson is getting better, hopefully he will be ready after the international break," he said.
If City beat Newcastle this weekend, they will remain in contention to win a second successive Premier League, Champions League and FA Cup treble.
In the Champions League quarter-final draw on Friday, they were once again pitted against Real Madrid after beating the Spanish giants in the semi-finals last year and losing at the same stage in 2022.
"It looks likes a little bit of tradition, three years in a row playing the king of the competition, who have won 14 Champions Leagues," Guardiola said.
"It is what it is. Hopefully we can arrive in a good moment. It's still a few weeks before the first game in Madrid. We will see."
On City's treble hopes, Guardiola added: "I don't think about that right now. In the last month of the season I will let you know.
"Now is a quarter-final against a top team in the FA Cup. Then we have the international break, we recover and play another final against Arsenal."