The Citizens will be without star midfielder Rodri (ACL) for the rest of the season, while young attacker Oscar Bobb is not expected to return until the end of the year as he continues to recover from a leg fracture.
Kevin De Bruyne has missed City's last six games with a groin problem and Kyle Walker was not involved in Sunday's 2-1 Premier League win at Wolverhampton Wanderers as he was not deemed 'fully fit' to feature. Pep Guardiola has since admitted that he "doesn't think" either player will be ready to return on Wednesday.
After missing seven games with a muscle injury, Nathan Ake watched on as an unused substitute against Wolves and the defender could be involved in some capacity against Sparta Prague, although he is not expected to start, so Josko Gvardiol - who scored a stunning 20-yard goal against Wolves - is set to continue at left-back.
As he did in City's 4-0 win against Slovan Bratislava three weeks ago, Guardiola could hand Stefan Ortega a start in goal at the expense of Ederson, while Manuel Akanji could take the place of either Ruben Dias or Sunday's match-winner John Stones in central defence. Rico Lewis, meanwhile, is likely to continue at right-back if Walker is not available.
In midfield, Guardiola may consider resting Mateo Kovacic and handing Matheus Nunes a start in a deeper midfield role alongside Ilkay Gundogan, while attacking midfielder Phil Foden will be hoping to force his way back into the first XI.
Savinho and Jeremy Doku both started on the flanks against Wolves, but Jack Grealish could replace one of those wingers on Wednesday. Bernardo Silva could also be deployed out wide, while Erling Haaland is expected to lead the line once again and will be seeking to avoid going three games without a goal.
Manchester City possible starting lineup: Ederson; Lewis, Akanji, Dias, Gvardiol; Gundogan, Nunes; Bernardo, Foden, Grealish; Haaland