The Premier League champions lost Ederson to injury, had second-choice Claudio Bravo sent off and ended up hanging on for a 1-1 draw against Atalanta with defender Kyle Walker in goal.
Ederson is now a doubt for Sunday's top-of-the-table clash with Liverpool while Bravo can hardly be full of confidence after a costly cameo, no matter how harsh his late red card at the San Siro seemed.
"Honestly, right now, I don't know (how bad it is)," said manager Pep Guardiola of Ederson's thigh problem. "He's strong and we'll try with him, but we won't take a risk."
City had looked on course for the victory that would have taken them through to the last 16 as winners of Group C after Raheem Sterling scored a sublime seventh-minute opener.
But the night took a turn for the worse after Gabriel Jesus tamely shot wide from the penalty spot just before half-time.
Ederson did not return for the second period and Bravo's first job was to pick Mario Pasalic's bullet header out of the net.
Atalanta grew in confidence and were chasing a late winner when Bravo was adjudged to have brought down Josip Ilicic.
There was an extraordinarily long delay as VAR checked referee Aleksei Kulbakov's decision to send Bravo off but it was eventually upheld.
Walker nervily saved the resulting free-kick from Ruslan Malinovskyi and City managed to see out the closing minutes.
"In this competition you know that when you have your moments you have to take it," said Guardiola.
"We made a good first half but ask the Italian teams how difficult it is playing against Atalanta. In the first half we were outstanding, in the second half we suffered a lot."
City, who are still five points clear at the top of the group, will now hope to secure their place in the knockout stages when they host Shakhtar Donetsk later this month.
Attention will now turn to Liverpool with the champions heading to Anfield hoping to cut into the Reds' six-point lead.
City are already likely to be without playmaker David Silva and they will now wait for updates on Ederson.
Should the Brazilian not make it, Guardiola has every confidence Bravo will be able to step up.
He said: "He's ready to play on Sunday. He's an incredible professional. If Ederson can play he will, but if not it will be Claudio."