Meanwhile, Shakhtar have started their domestic campaign with seven successive victories, form which suggests that they could pose a threat to the Premier League champions.
Pep Guardiola would have hoped to have begun the club's latest attempt to win European football's premier competition while remaining in close proximity to Liverpool in the Premier League, but Saturday's setback at Norwich has provided the Spaniard with a different perspective.
While the top-flight champions have been given a favourable group, Guardiola now finds himself needing to find a much-needed solution at the back due to lack of stability in the defensive third.
Guardiola will hope that Nicolas Otamendi can rediscover the form that he produced at the start of his stint at City, although the visit to Ukraine may be regarded as an opportunity to try a fresh system away from the intensity of England's first tier.
On a positive note, there remain few issues with an attack which continues to create chances and score goals on a regular basis, with Raheem Sterling and Sergio Aguero already having a dozen strikes between them in the league.
Despite the travelling time involved, Guardiola may also welcome facing Shakhtar for a third season in succession, a task which should provide few surprises for his squad.
City registered a routine 3-0 success last year, but Shakhtar may pose a stronger test this time around having put together seven victories on the bounce on the domestic front.
The forward has now netted seven times in as many outings since the end of July, with midfielder Marlos also chipping in with five efforts of his own.
Shakhtar Donetsk form: WWWWWW
Manchester City form: DWDWWL
Guardiola will almost certainly hand a recall to Kevin De Bruyne, who was only named among the substitutes for the defeat at Carrow Road.
The City boss may also look to get Joao Cancelo involved after his big-money switch from Juventus, with the Portugal international potentially playing at right wing-back if Kyle Walker is moved in-field.
Benjamin Mendy could also come into contention after Guardiola spoke of the left-back's progress from a knee injury ahead of facing the Canaries.
Shakhtar Donetsk possible starting lineup: Pyatov; Bolbat, Krivtsov, Matviyenko, Ismaily; Stepanenko, Alan; Konoplyanka, Marlos, Taison; Moraes
Manchester City possible starting lineup: Ederson; Walker, Fernandinho, Otamendi; Cancelo, Rodri, De Bruyne, Zinchenko; B.Silva, Sterling, Aguero
We say: Shakhtar Donetsk 1-3 Manchester City
While City are having to contend with defensive issues, it would come as a surprise if they do not get three points on the board on Wednesday night. Shakhtar have the quality to pose a threat going forward, although they may struggle to keep their opponents out at the other end.
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