City duo Micah Richards and Gareth Barry are set to miss Sunday's glamour game, with the latter facing up to a month on the sidelines, while captain Vincent Kompany will undergo a fitness test 24 hours before the game.
Italian striker Mario Balotelli and Spanish midfielder David Silva, who both starred at Euro 2012, will feature from the bench after only beginning their pre-season preparations six days ago following extended leave.
have a fully fit squad to choose from ahead of the clash at Villa Park, including new signings Eden Hazard and Marko Marin.
The stadium was chosen to host the game as Wembley is unavailable due to the Olympic men's final between Brazil and Mexico on Saturday.
"It's certainly hard to stay at the top," Di Matteo said. "There'll be a lot of good teams this season. The Premier League is getting more balanced every year.
"They have a good squad and they will be difficult to catch, but that's the job of all the other teams - to try and win against Manchester City."
However, the Italian did admit it will be tough for his side to challenge the two Manchester sides this season having finished 25 points behind them last season.
"There's been a big gap last season, and that is one of our challenges this season, to bridge that gap," Di Matteo said. "25 points are a lot of points, with both Manchester teams.
"It'll be a tough season ahead but we'll try and compete."