City manager Pep Guardiola has revealed the veteran Spanish playmaker suffered a muscular injury in the champions' hard-fought Premier League win over Southampton on Saturday, and is likely to miss out against the Reds.
Silva did not return for the second half at the Etihad Stadium after sustaining the problem in the latter stages of the first period, and the City boss was not optimistic after the game.
City will need to do further tests, but even if the injury is nothing serious, the trip to Anfield will still come too soon.
"David Silva was injured. Five minutes before the first half ended he told me he had a muscular problem," Guardiola revealed after the win.
"When he has a muscular problem and cannot play more minutes it is because he has something and when it is a muscular problem it is always a minimum of 10-12 days."
That would rule out the 33-year-old, who is in his final season at City, until after the international break.
City travel to Italy to face Atalanta in the Champions League in midweek before travelling to Anfield on November 10.
Guardiola's side trail the Reds by six points heading into that game.
Liverpool have not been beaten in the league since their loss at the Etihad last January and their last home defeat came in April 2017.
They have dropped just two points this term.
It is undoubtedly a key fixture in the title race but, with so much of the season remaining, Guardiola does not see it as must-win.
"We are going to try but I don't think so. How many centuries and they don't lose at Anfield? We will see," Guardiola added.
"Now we go to Italy and when we come back we go to Anfield. Many things are going to happen and there are a lot of games to play."