A knee injury has seen De Bruyne ruled out of action since the start of November. It is second knee problem of the season and the Belgian has been limited to only three Premier League appearances totalling just 81 minutes as a result.
Aguero, meanwhile, hasn't played since scoring in last month's 2-2 Champions League draw with Lyon because a muscle problem and has been forced to miss the recent Premier League wins over Bournemouth and Watford.
"No, both cannot play tomorrow. Both will be back soon," Guardiola told the gathered media on Friday, via ManCity.com, when he attended his weekly press conference.
Vincent Kompany and Oleksandr Zinchenko are doubts for the game. Fabian Delph will likely replace the latter at left-back given that Benjamin Mendy is a long-term absentee.
City remain two points clear of Liverpool at the top of the Premier League table after winning 13 of their opening 15 games in defence of the title they won by 19 points last season. Early contenders Chelsea have fallen away after managing to win only one of their last four games.
City's form had led Chelsea boss Maurizio Sarri to label the Sky Blues the best team in Europe, although Guardiola is keen to downplay such a statement.
"Thank you [to Sarri] but we are not the best We have to win the titles and we didn't win the titles to be best team in Europe. Thinking that it's not necessary to improve, that would be the most dangerous thing. We can do better," the City boss replied.