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Citywon eight of their last 10 league matches and despite finishing 18 points behind champions Liverpool, Pep Guardiola's side have plenty of momentum behind them heading into the clash.
Both managers have practically their entire respective squads at their disposal, although City are without the suspended Benjamin Mendy whilstSergio Aguero remains a major doubt after having kneesurgery in June.
Madrid are without suspended captain Sergio Ramos andforward Mariano Diaz is unavailable.
The visitors to the Etihad stadium know they must score at least twice to have any hope of making it through and Madrid have a strong recent pedigree on the road in the competition.
High-profile wins at Juventus, Paris Saint-German, Bayern Munich and Borussia Dortmund in recent years will give the side confidence, although their most challenging road trip in this season's competition saw them beaten 3-0 in Paris.
However, this is a very different Madrid side to the one that started the season, with a newfound defensively solidity that hasserved them well domestically on their way to the title.
Whether they can keep a City side that racked up 102 Premier League goals this season at bay remains to be seen, especially without Ramos, but there is a resilience to this Los Blancos team which was not there in previous seasons under Zidane.
Of course they could win and still get knocked out, yet the odds foran away win will surely tempt plenty given the side's pedigree in the competition.
Odds correct at the time of writing. Please gamble responsibly.