The Argentine came off in discomfort 12 minutes into Saturday’s 2-0 win over Fulham having scored City’s second and Pep Guardiola has confirmed he will not be fit enough to face Neil Warnock’s side.
He joins Fabian Delph and long-term absentee Claudio Bravo on the sidelines.
“He didn’t train last two days, tomorrow he is not able to play," Guardiola said. "Maybe Saturday [against Brighton] but we will see in the next days.
“Aguero and Fabian Delph [are the only ones who are injured]. The others are quite well.”
With City still on course to win an unprecedented Quadruple, Guardiola knows his side face a crucial period of fixtures between now and the end of the season.
City have already lifted the Carabao Cup, secured a place in the quarter-finals of the Champions League and have Saturday's FA Cup semi-final against Brighton at Wembley to look forward to.
Guardiola says it’s a privilege to still be involved in all four major competitions, but has warned his players that any dip in performance over the coming weeks will see City lose everything.
"No one said it would be easy," he said. "We know it.
"Yesterday I saw how good Arsenal are playing. We have an incredible distance [from Arsenal] because we have done so well.
"Everyone is excited about the next weeks but we also know we can lose everything. It’s not complicated.
"It’s amazing to have this opportunity, to be there.
"Beating Cardiff is our main target, then we go to Wembley and we want to win a trophy I have never won, the oldest one."