Saka was a fitness doubt heading into Tuesday night's Champions League group game at Lens, which saw them go ahead against the run of play only to collapse to a 2-1 defeat to see their unbeaten start to the season end.
Arsenal played most of the game without Saka, who was forced off in the 34th minute and replaced by Fabio Vieira who struggled thereon. Speaking after the game, Mikel Arteta said Saka "tried to backheel the ball and felt something, it was something muscular."
The Gunners now face the very real prospect of playing one of their toughest games of the season without their talisman as Premier League champions City come to town on Sunday. Henry wants three players to take responsibility in Saka's absence.
"People were talking about Rodri not playing at the weekend now suddenly you don’t have the main man at Arsenal in my opinion playing against Man City at the weekend. We’re not going too far, but it looks like it.
"It’s going to be the job of an Eddie Nketiah, a [Leandro] Trossard or the job of a Kai Havertz who came to show that we’re not going to think about Bukayo if he’s not playing at the weekend.
"The only thing you can say about Bukayo is he’s been playing everything and at some point you are going to hit the wall and it’s going to be too much.
"I don’t know what happened tonight but obviously he is going to be missed. How long it will be I don’t know, but we need to find a way to beat City because we haven’t done that for a very long time in the league."