Mancini expected a stern examination of City's unbeaten league record even before Roman Abramovich pulled the plug on Di Matteo's short reign this week.
Instead of his fellow Italian it will be Rafa Benitez in the adjacent dugout, and the City manager said: "Usually when one team changes a manager the game after for the opponents is very difficult. For us, I think it is more difficult.
"Chelsea is a good team with Di Matteo and will be a good team for Benitez. They have good players. Until three games ago they played fantastic football and were on the top."
The decision to sack Di Matteo has drawn near-unanimous criticism from his fellow managers, and Mancini is no different.
He said: "I am very sorry for Di Matteo because he won the Champions League three or four months ago - but this is our life.
"When we make this choice to become a manager we know it can also be difficult. It is difficult for him, but this is the manager's life."