Home side more injury troubled
Following a tough start to the season on the injury front, Pep Guardiola's side have remained relatively trouble-free in recent months.
The Blues again have no fresh injury concerns ahead of this one, with Claudio Bravo the only long-term absentee, whilst Vincent Kompany and Benjamin Mendy near returns following their lengthy layoffs.
The home side, however, have had some injury problems since returning from their winter break.
The Miners are expected to be without Steven Skrzybski, Alessandro Schopf and Benjamin Stambouli, as these three players have missed the past four games with injuries.
Breel Embolo has been a long term absentee with a fractured foot and will also miss the visit of one of the Champions League favourites.
Schalke 04 predicted XI: Fahrmann; Caligiuri, Sane, Nastasic, Oczipka; Bentaleb, McKennie, Harit, Konoplyanka; Kutucu, Burgstaller.
Man City predicted XI: Ederson; Walker, Stones, Laporte, Zinchenko; De Bruyne, Fernandinho, Gundogan; Sterling, Sane, Aguero.
Quadruple still on
Following victory over Newport County at the weekend, City remain in contention to achieve an unprecedented quadruple this season, with a Carabao Cup final to play later in the week, and still being well in the hunt for the Premier League and Emirates FA Cup.
Domenico Tedesco's men also remain in the DFB-Pokal as well as the Champions League, although will be most disappointed with their league campaign.
Schalke finished second last season, although have had a season to forget in the league so far, as the side from the Veltins Arena have won just one of their last five, and currently sit 14th, 18 points off the top four.
Strong group stage campaigns
Despite differing league form, both of these teams endured a successful group stage campaign.
The champions of England lost their opening game before going on to top their group - winning four of their next five games.
Die Konigsblauen also only lost one of their six games, finishing second, only behind FC Porto, meaning both sides will go into this one with confidence.
City's sole focus will be to get a few away goals, making their job as easy as possible in the second-leg at the Etihad, potentially allowing them to turn their focus elsewhere as the fixtures continue to pile up.