Both players were injured on international duty with England.
Walker was replaced early during a 1-0 defeat to Brazil with a hamstring problem, while Stones limped off in Tuesday's 2-2 draw with Belgium due to an adductor issue.
Defending champions City are third in the Premier League, but just one point behind leaders Arsenal, who are ahead of Liverpool only on goal difference.
The absence of the key defensive duo is also a worry for City with the first leg of their Champions League quarter-final away to Real Madrid on April 9th.
"Kyle's (injury is) more tough than John's but they will be out - I don't know for how many games," said Guardiola at his pre-match press conference on Friday.
However, there was more positive news for Guardiola as Ederson, Manuel Akanji, Jack Grealish and Kevin De Bruyne all look set to return from injury.
De Bruyne, who sat out City's 2-0 FA Cup quarter-final win over Newcastle before the international break, has suffered an injury-plagued season after missing the first five months of the campaign with a hamstring tear.
However, the 32-year-old has provided 12 assists and scored twice in 12 appearances for City this season when fit.
"Kevin is so important," added Guardiola. "It has been a tough season for him with injuries.
"He has been out for a long time but he trained really well yesterday. We will see what he does in the next days."
De Bruyne scored twice in City's 4-1 win over Arsenal at the Etihad last season which proved a telling blow to the Gunners' title aspirations.
Mikel Arteta's men look like a more mature and well-rounded force this season, but face the acid test of whether they are ready to dethrone City as English champions on Sunday.
City have not lost at home in 38 games in all competitions, stretching back to November 2022.
Guardiola's men also remain on course to repeat their treble triumph of last season.
The winners of City's Champions League tie against Madrid will play either Arsenal or Bayern Munich in the last four.
City also face Chelsea in the FA Cup semi-finals next month.
"This season has been really good," said Guardiola.
"To be in contention for the three important titles now, we've done incredible work.
"Now it's the last 10 games of the Premier League, we start an important time. We play the leaders of the Premier League and I'm sure the people (City's fans) will give us what we need to perform at our best."
