Vincent Kompany, Joe Hart and Yaya Toure are doubts to face Borussia Monchengladbach, giving Manchester City manager Manuel Pellegrini a Champions League injury headache.
Last season's Premier League runners-up got the campaign off to an exceptional start but have begun to stutter recently, losing three of their last four matches in all competitions.
A 2-1 home defeat to Juventus in their Group D opener heightens the importance of winning on Wednesday, although they will be without a string of key players in Germany.
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David Silva, Eliaquim Mangala and Fabian Delph all missed Saturday's 4-1 loss at Tottenham, as did Wilfried Bony, Gael Clichy and Kelechi Iheanacho.
Things got worse at White Hart Lane as Toure came off with a hamstring complaint and an ongoing calf issue saw captain Kompany withdraw from the squad before kick-off.
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Hart was reduced to a role on the bench due to a back problem, adding to City's problems ahead of the trip to Monchengladbach.
"Joe had a problem with his back during the week," City boss Pellegrini said.
"He could train just one day this week, that's why I decided to play (Willy) Caballero. Joe was not 100-per-cent.
"Yaya had some problem with his hamstring.
"We don't know (if they will be fit). We must wait for Sunday or Monday to decide if they are 100-per-cent."
The prognosis on centre-back Kompany seems more clear-cut, though.
"I don't think (he will be available on Wednesday)," Pellegrini said. "At the beginning he was fit to be on the bench.
"In the warm-up, he felt also some problem in his calf. We will see in the way he developed the next few days."
City struggled without Kompany, Toure and Hart as Kevin de Bruyne's first half goal was wiped out at White Hart Lane.
Eric Dier, Toby Alderweireld, Harry Kane and Erik Lamela netted as Pellegrini's men suffered a 4-1 defeat, but the City boss dismissed suggestions he side lacked leaders.
"No, I never complain about players that cannot play," he said.
"I think this team played very well in first 45 minutes and maybe deserved a better score.
"After that, two set pieces and that's not about leaders. It is about marking, concentration. That decided the game."
While City look to right some wrongs in Germany, Spurs will try to kick on against Monaco this Thursday - a Europa League tie in which goalscorer Dier hopes they can get another big result.
"It was a great result," the defensive midfielder told Spurs TV. "Everyone is really happy.
"I think it has been a long time coming, really, that we get a big result like this.
"We've been working very hard and the last couple of results - minus the Arsenal one - have been good, so everyone is really happy."