Aguero, who has scored 19 goals in 20 Premier League and UEFA Champions League games this season, limped out of Saturday's 1-0 win over Everton after straining knee ligaments.
And, on the eve of City's decisive European showdown at the Stadio Olimpico, manager Manuel Pellegrini has revealed the timescale of the Argentina striker's recovery.
"He is injured," said Pellegrini. "He will not be playing."
"He will be out for four to six weeks. His recovery will depend. But our team does not depend on one player."
Pellegrini, who confirmed that Edin Dzeko will lead the City line against Roma, also revealed Kompany and Silva could return from injury.
The Belgium defender has missed the last two games due to a hamstring problem, while the Spain playmaker has not appeared since October because of a knee injury.
"They are here," he said. "They will be assessed tomorrow."
After a dramatic late comeback snatched a 3-2 win at home to Bayern Munich last time out – a result that left City in with a chance of progressing from Group E – Pellegrini is optimistic they can complete the job.
"It is an important game," he said. "We have a good squad. We have made mistakes in the other games but we are fighting to qualify.
"If we can [beat] Bayern Munich, we can do it again tomorrow."
