United clash 'life or death' for Bayern
The Bavarian giants suffered their first Bundesliga defeat since October 2012 on Saturday as their 53-match unbeaten league run was ended when they lost 1-0 at Bavarian rivals Augsburg.
With one eye on the quarter-final, second leg at home to United, and with the Bundesliga title already secured, Guardiola paid the price for naming a weakened team.
Having drawn the first-leg 1-1 at Old Trafford, David Moyes' United will face a different Bayern team at Munich's Allianz Arena, but the Augsburg result leaves the European champions winless in their last three games.
"Sooner or later we had to lose, we accept that and we have to prepare as quickly as possible for Manchester United," said head coach Guardiola.
"Next Wednesday is a final for us. It's a matter of life or death."
Guardiola started with three teenagers at Augsburg, giving Bundesliga debuts to wing-backs Ylli Sallahi and Mitchell Weiser while Pierre-Emile Hoejbjerg was named on the left wing.
The gamble backfired when Weiser lost possession to Augsburg's Daniel Baier who fed Sascha Moelders and the Augsburg striker blasted his shot past Bayern's goalkeeper Manuel Neuer with 31 minutes gone to claim the winning goal.
"We tried everything and fought until the end," said Guardiola.
"We have no complaints, we lost because the opponent was better than us. That's football. You can't always win."
He could have easily fielded a stronger side and after his team went behind for the third match in succession, Guardiola responded by bringing stars Mario Goetze, David Alaba and Thomas Mueller off the bench.
Left-back Alaba hit the post with 68 minutes gone, while Goetze and Muller went close as Bayern pushed in vain for the goal to keep alive hopes of becoming the first team to go through a Bundesliga campaign undefeated.
"That hurts a bit," admitted midfielder Mueller.
"We wanted to defend our unbeaten run, but we just didn't produce on the pitch what we are capable of. The fact is that it's never easy to win at Augsburg, but it was not the plan to go home with a defeat."
Both Javi Martinez and Bastian Schweinsteiger are suspended for the United clash, meaning Toni Kroos and captain Philipp Lahm are likely to pair up in the defensive midfield.
Goalkeeper Manuel Neuer said the main thing was to come through the Augsburg match without injuries.
"We took Augsburg seriously, but the main thing is that no-one is injured," said Neuer as Bayern failed to score for the first time this season in all competitions.
"It's all about Wednesday and the game against Manchester, nothing else matters."
Having lost 4-2 at Borussia Dortmund in July's German Super Cup final and beaten 3-2 at home to Manchester City in the Champions League group stage last December, this was only Bayern's third defeat of the season.