Otamendi was sent off for a second bookable offence in City’s dramatic 3-2 first leg win at Schalke’s Veltins Arena and will serve a one-match European ban.
Fernandinho will also serve a one-match ban, though the midfielder picked up a groin injury in Gelsenkirchen which rules him out regardless.
Aymeric Laporte has returned to training having recovered from a hamstring injury and could replace Otamendi in the centre of Pep Guardiola’s defence.
John Stones, who is a doubt with a groin problem, trained with the first-team squad on Monday but Vincent Kompany was not present.
Kevin De Bruyne remains sidelined with a hamstring injury and second-choice goalkeeper Claudio Bravo is a long-term absentee.
Schalke are without midfielders Alessandro Schöpf (knee), Omar Mascarell (groin) and Daniel Caligiuri (ankle).
Manchester City: Ederson; Walker, Stones, Laporte, Zinchenko; Bernardo, Gundogan, Silva; Sterling, Jesus, Sané.
Schalke 04: Fahrmann; Stambouli, Sané, Nastasic; Mendyl, Bentaleb, Serdar, McKennie; Embolo, Skryzbski; Burgstaller.
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