Tottenham manager Mauricio Pochettino has admitted that striker Harry Kane could be out for the rest of the season.
In the 55th minute, the Spurs star attempted to block a clearance by Fabian Delph and the City defender inadvertently stepped on Kane's ankle as he was following through.
Kane immediately had to be helped down the tunnel, unable to put any pressure on his troublesome left ankle.
The Tottenham star was replaced by Lucas Moura, with the Brazilian coming off the bench in the 58th minute of a scoreless quarter-final first leg.
Spurs went on to win the match 1-0, getting a 78th-minute goal from Son Heung-Min to give them the advantage ahead of the second leg.
But the win came at a cost, as the Spurs boss said after the game that Kane may have played his last match this season.
"It's very, very sad. It's going to be tough and we're going to miss him - maybe for the rest of the season," Pochettino told BT Sport.
Kane was out for six weeks after suffering torn ankle ligaments in a loss to Manchester United on January 13.
With the calendar having shifted to April, Kane appears to be facing a difficult comeback to make it back before the end of the season.
Spurs have six Premier League matches remaining, with Mauricio Pochettino's side holding onto the fourth and final Champions League spot, one point ahead of fifth-placed Arsenal.
Kane will also miss Tottenham's return leg against Man City, which will take place next Wednesday at the Etihad Stadium.
The 25-year-old is in the middle of another strong campaign, having scored 24 goals in 38 appearances in all competitions for Spurs in 2018-19.