The England goalkeeper returns to the starting XI for Manuel Pellegrini's side, who have qualified for the knockout stages and romped to a 6-0 victory over Tottenham on Sunday
The Premier League outfit have already secured their place in the last 16 but will be hopeful of building on back-to-back victories over CSKA Moscow in Group D, having never won three consecutive games in the competition before.
Manuel Pellegrini's men may have won just three of nine matches on the road this season but their home form has been terrific. Of their nine games at the Etihad Stadium, eight have finished in wins, with City scoring an outstanding 37 goals in the process.
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Aguero has scored 14 goals in his last 11 matches in all competitions for City and has an excellent record in the Champions League, with seven in his last six appearances.
Samir Nasri is joint first in Champions League assists this season, with the Frenchman having four to his name, and Alvaro Negredo is also in great form, scoring a hat-trick in their 5-2 success over CSKA Moscow earlier in November.
Romania goalkeeper Costel Pantilimon has played the club's last five matches as first choice Joe Hart spent an extended period on the sidelines after suffering a loss of form.
Pellegrini confirmed on Sunday that Hart would start on Wednesday and he will be hopeful of keeping a clean sheet with the significant attention that will be on his performance, while City are likely to be without captain and centre-back Vincent Kompany (thigh).
Viktoria Plzen sit bottom of Group D without a point from four matches and have conceded 12 goals. Their 5-0 loss at Bayern Munich was their worst in the Champions League but they have had better results domestically, with a 3-1 win at Zbrojovka Brno on Friday keeping them second in the Czech top flight. Stanislav Tecl scored twice in that match, giving him eight in 11 starts this season.
Plzen coach Pavel Vrba will take charge of his penultimate Champions League match with the club after agreeing to take on the Czech Republic job. Vrba will lead the Czechs through qualifying for Euro 2016 after triggering a release clause in his contract earlier in November.