City have enjoyed a remarkable season so far, and lead the Premier League by 13 points ahead of Sunday's trip to Crystal Palace.
Guardiola's squad are also through to the last 16 of the Champions League, and the Carabao Cup semi-finals, and begin their FA Cup campaign next weekend.
"I am worried about that," said Guardiola. "Four competitions, I don't know if we will be able to do that.
"The schedule - you have to be careful. I am worried because we cannot play every three days.
"We cannot play Kevin De Bruyne every three days [for] 80 minutes, 80 minutes. He needs to be refreshed to help in the last part of the season.
"I have never before been in this situation. Three competitions I have handled many times, but four never.
"And the fourth is double games [two legs], and extra time. We are going to see how we handle that situation."