The Argentina missed the 3-1 victory after playing against Lyon in the Champions League during the week.
And Guardiola says the decision was made by the club's medical staff.
"The doctors told me Sergio cannot play," Guardiola told his pre-match press conference before Tuesday night's trip to Watford.
"If he plays, maybe four or five weeks off. In that situation this month, with a lot of games, he was not safe.
"It's going to happen in the future, in the next games. People will start to be tired in a lot of games. That's why we have a deep squad."