Silva, who scored the pivotal winner against West Ham United on Sunday, was left out of the City squad that travelled to Kharkiv for their final Champions League group game against Shakhtar Donetsk.
Guardiola is expected to rest some members of his first-team squad with his side already qualified for the knockout stages of the competition as group winners but speaking at a press conference ahead of Wednesday's [6 December] clash, he revealed the decision to leave Silva back in Manchester was an enforced one.
"David Silva has a little problem – I don't know whether he will recover for Sunday," Guardiola said. "He felt uncomfortable after his goal [against West Ham]. He felt something. Hopefully he can play on Sunday."
Kevin de Bruyne is another who has not made the journey to Ukraine with the Belgium international set to serve a one-match suspension after picking up three yellow cards in the group phase of the competition. Bernardo Silva is set to start in his place.
City's late win over West Ham reopened an eight-point advantage over second-place United in the Premier League title race and extended their winning run to 13 games – equalling records previously set by Chelsea and Arsenal.
Silva, who last month signed a one-year contract extension until 2020, has been sensational in that run, scoring twice and laying on eight assists as Guardiola's side have set about dismantling Premier League opposition at will.
City will already be without John Stones for their trip to Old Trafford, with the England international sidelined with a hamstring problem he hopes to return from in time for the Christmas period. Benjamin Mendy is the club's only long-term absentee as he continues to recover from an anterior cruciate ligament injury.
A win will see City break a Premier League record for most consecutive wins while at the same time shatter United's unbeaten record at home – which will stretch to 40 in all competitions if they avoid a loss to CSKA Moscow on Tuesday [5 December] night.
A win for United meanwhile will see them become the first side to halt Guardiola's men this season. "We just play to win the game," Guardiola said. "I assure you, sooner or later we will lose, but the next day we will recover. I can promise you we are going to try to win this game."