City, second in Group A behind Paris Saint-Germain, can take a giant step towards the knock-out rounds with victory over the Belgian side at the Etihad Stadium on Wednesday.
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The clash comes three days before facing Manchester United but Guardiola said the stakes will be higher against Brugge.
"This game is much more important than the United game," Guardiola told a news conference on Tuesday. "It would be an incredible step forward to qualify for the last 16 of the Champions League.
"In the Premier League there are many games, here just six, now three left. Not much and they are decisive, the third and fourth games. These are the most important games and we need to take it seriously.
"Tomorrow we have a chance, every year is more difficult. It's just six games, lose more than one or two it's difficult and we already lost in Paris."
They haven't gone three games without a win since December 2018 but Brugge will need a significant change of fortune after losing 5-1 in their first meeting in Belgium two weeks ago.
"We make incredible runs, 100 points, 98 points, last season 21 wins in a row," Guardiola added. "Never at the start I think we win 21 in a row.
"We are focused on winning against Brugge, it depends on doing many good things to give you the chance to win games.
"We are still making mistakes, defensively the back four, the pressing. It's normal. I saw the game against Brugge and I thought how many bad things we did. After the game I thought how good it was. Offensively we did it.
"I'm pretty sure they will adjust things to punish us. We have to adjust to get better. It's normal, it will be a completely different game."
Guardiola, meanwhile, has also backed Kevin De Bruyne to rediscover his best form after a relatively slow start to the season by his high standards.
The midfielder has been hampered by injuries -- he picked up a significant ankle problem during Euro 2020 -- and struggled against Palace but Guardiola is convinced the loss of form is only temporary.
"You cannot imagine how good a player he is," the City boss said. "When you have a long career like him, you have highs and lows. He's training and knows he has our complete support.
"I was a player I know all the time you cannot perform incredibly well. He knows better than anyone he can do better, we are with him, I know what he's doing every day to get back to his best.
"Sometimes the fatigue takes its place. We are sitting here and see all the players have to make their best performance every three days. No human being can do it."