After a 0-0 draw against Chelsea in the semi-final first leg on Tuesday, a victory or a score draw in London would assure Atletico of a place in their first European Cup final for 40 years.
Atletico have been a model of consistency this season under coach Diego Simeone's "match by match" strategy and their progress in three competitions, having also reached the Copa del Rey semi-finals, is all the more remarkable considering their limited squad.
Tired legs will be the main concern as they prepare for the difficult visit to Valencia's Mestalla, and they cannot afford to rest players, admits Simeone:
"We are in good spirits and motivated to wear the Atletico Madrid shirt. We are in privileged position.
"We are only thinking about Valencia now and then we will consider next Wednesday (against Chelsea)."
Atletico lead the way in La Liga with 85 points, four more than Barcelona and six ahead of Real Madrid, who do have a game in hand.
However, a slip-up against Valencia would be costly especially as they still have to face Barcelona away on the final day of the season.
Comparing the two sides' records makes for interesting reading:
They have similar passing stats, both in terms of numbers and accuracy, and create a similar number of chances. They also make a similar number of tackles and blocks, with a similar success rate.
However Atletico are notably more effective at converting those chances (21%-13%), and are far superior defensively (22 goals conceded to 47).
Personnel is key here, as in Diego Costa Atletico have one of the best strikers in Europe; but coaching is vital too, with Simeone building a combative team in his own image, a team that defends and fights as a unit.
That scrappiness could well prove the difference against Valencia. But, with Atletico matches tighter than most, anything could happen.
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