Mustafi has been out of action since he suffered a groin problem, whilst away on International duty with Germany at the beginning of the month.
There was a glimmer of hope coming from the Arsenal camp that the German could be back in time for the trip to the Etihad Stadium this Sunday, but those hopes are vanishing as each day passes.
It now looks most likely that Arsene Wenger and the medical staff will target the North London Derby, which follows after the next international Break, as Mustafi's return date.
Arsene Wenger could have really done with Mustafi returning to the first-team this week, as the Gunners have yet another big few days ahead of them.
Firstly, Wenger's side welcome Serbian outfit, Red Star Belgrade to the Emirates Stadium on Thursday evening in the UEFA Europa League, where Arsenal can all but confirm their passage through to the knockout stages.
Then the daunting mission of an away trip to runaway leaders City follows a couple of days later in the Premier League. Mustafi's absence is set to leave Wenger with a defensive headache in the coming days.
Light in numbers at the back
Before the season started, Arsenal were already rather short on defensive options, especially after the sale of Gabriel Paulista to Valencia in the summer.
Mustafi has become an integral part of that back three which Wenger has adopted, though with the German missing it has left the Gunners even shorter at the back.
Per Mertesacker has been filling in for Mustafi whilst sidelined, and with Mertesacker heading in to his final season in professional football before his retirement next summer, it is proving a rather demanding time for Arsenal skipper.
Wenger has also been given a scare with the fitness of Sead Kolasinac, after the Bosnian limped off towards the end of Arsenal's 2-1 win over Swansea on Saturday.
It is yet to be confirmed whether or not Wenger will risk Kolasinac ahead of Thursday's European encounter, with the Arsenal boss' eyes firmly fixed on Sunday's game in Manchester.