Midfielder Samir Nasri will miss the game against his former club, however, after suffering a hamstring injury against Real.
Argentine Aguero has not played since injuring his knee on the opening weekend of the Premier League season against Southampton but was an unused substitute in the Bernabeu on Tuesday when City conceded twice late on to lose 3-2.
"Sergio is fit," Mancini told a news conference on Friday. "I wanted to put him on in the Bernabeu but we had a couple of injuries."
The visit of in-form Arsenal will be a stern test for City who have started the defence of their title in steady, if unspectacular, fashion.
City have eight points from their first four games, four fewer than at the same stage last season when they began in barnstorming fashion, scoring 15 goals in four games and conceding three. This time they scored nine and conceded six.
Mancini admitted it had been a difficult start, saying the European Championship had reduced the preparation time.
"We have conceded a lot of goals and I don't think it's our real defence at the moment," he said. "We need to improve."
"I think Arsenal can compete for the title this year," he said. "I don't know if they're better than last year but they have less pressure. They lost two or three important players but they will play for the title.
Mancini rubbished reports of a rift with Mario Balotelli despite leaving the controversial striker out of the squad against Real.
"There has been no argument, and no row. Absolutely not," he said. "Mario went in the stand only because we started to play with Carlos Tevez in attack and we couldn't have three strikers on the bench."