Last season, Palace ended City's record 18-game winning run last season but Guardiola's team still amassed 100 points as they cruised to the title.
A visit to Selhurst Park would therefore be a tricky fixture for City at the best of times, but the timing, between the two legs of a Champions League quarter-final against Tottenham, adds an extra layer of difficulty.
"I'm so pleased", Guardiola said.
De Bruyne told Sky Sports: "We know if we don't win the Premier League people will say it's a failure, but we can only try and perform well, and even if we don't make at the end, I think we will have had a great season, but we obviously want to win and we will see how far we go".
Guardiola's upbeat attitude, despite a first defeat in 15 games, suggests a longer-term plan to keep his squad as fresh as possible for a gruelling run-in.
The champions' return to the top of the table extended to only a few hours on Sunday before Liverpool rescaled the summit with victory against Chelsea.
And former Premier League striker Efan Ekoku knows it can be hard to ignore the pressure.
McArthur made way for Bakary Sako for Palace, John Stones replacing Sane for City, who removed any lingering doubts about the result when Jesus kept his cool after De Bruyne had played him into the area. Guardiola knows all too well what can happen at old, historic grounds like this when the home team - and their fans - are up for the fight.