City head into the fourth-round clash at the Etihad Stadium in blistering form, having gone 18 games unbeaten in all competitions.
Pellegrini's men will attempt to extend that run on Saturday, but will have to do so without the Spanish duo.
Silva is rested because of a hamstring problem, while Negredo has been left out due to a shoulder injury sustained in the 3-0 (9-0 agg) League Cup semi-final win over West Ham on Tuesday.
However, the Chilean is confident that neither player will be out of action for long.
"Silva is not 100 per cent so will be rested and Negredo has a shoulder problem. We will see how Alvaro is over the weekend," Pellegrini said.
"Silva has a small problem with his hamstring - nothing too serious - but he won’t play tomorrow as a precaution.
"The initial opinion on Negredo's shoulder injury is that it is not a serious problem. The rest of the squad is available."
Watford sit a disappointing 15th in the Championship - 10 points adrift of the play-offs - but Pellegrini is expecting a determined effort from Giuseppe Sannino's side.
He added: "Watford may not be having a great season but they will be motivated when they play us because this is the FA Cup."
