De Bruyne came off the bench in Saturday's 5-0 win over Burnley to make his return after two months out with a knee injury, while Kyle Walker missed out on the game at the Etihad with a groin problem.
Guardiola spoke ahead of the game on the availability of his squad. "If they are here it is because they are ready to play."
The Catalan was high in praise for experienced duo David Silva and Fernandinho, saying he wanted the pair to stay at City for as long as possible.
"They have two more years contract but they have to think day by day, month by month and then ask themselves at the end of the season if they are still ready to play. My advice then is to play, you have to play.
With City having lost their first Champions League fixture against Lyon, Guardiola wanted his side to continue to learn from their mistakes.
"Learn from that [defeat]. When you play an entire season the Champions League level is higher. So work. It looks easy, it is not.
"When you win games with a big result it is not easy. So learn, you have 15 points still to play for and to compete in the competition you have to live it. All we can do is learn and try to avoid it in the future."