LONDON (AP) -- Despite Barcelona and AC Milan stressing the need to avoid complacency to reach the Champions League quarterfinals, there should really only be two matches this week where the outcome remains uncertain.
Benfica hosts Zenit St. Petersburg after a 3-2 loss in Russia and newcomer APOEL will be trying to overturn a 1-0 away loss to Lyon.
But although Barcelona has a 3-1 lead over Bayer Leverkusen, the holders will have to cope without injured strikers Alexis Sanchez and David Villa at the Camp Nou on Wednesday.
And Leverkusen, with nothing to lose, is full of confidence after securing its first league win over Bayern Munich in 15 attempts at the weekend.
"Some may take Leverkusen for granted and underestimate them," Barca coach Pep Guardiola said. "But we still have a lot of work to do to get ready for a team with a lot of height that with a corner kick can break open the knockout series."
And since losing the first leg to Barca, Leverkusen has won three league games in a row for the first time this season.
"This is a very young team that tries to play with a lot of passion," Leverkusen coach Robin Dutt said. "They are always moving and are prepared to run a lot."
But top scorer Lionel Messi should be well rested after sitting out Barcelona's 3-1 win over Sporting Gijon due to suspension on Saturday.
The three-time world player of the year has netted seven goals in the Champions league and 43 overall for Barcelona this season and scored his first hat trick for Argentina last week.
And Dutt knows his side will need to produce an extraordinary performance in Spain.
"The way they pass the ball is second to none," he said. "But every once in a while they draw a match, every once in a while they lose."
AC Milan would have to collapse like no side has in Europe since the 1980s to be ousted by Arsenal after a 4-0 victory in Italy.
"We know the statistics are against us, but you also know that you can realize the impossible when you don't know it is impossible," Arsenal manager Arsene Wenger said. "We can score in quick succession and we can have a good edge in our game. We have it all to win, and all to do because the result is written before we turn up, but we can change it, and we must go for it."
And Milan coach Massimiliano Allegri is not taking anything for granted. After all, Milan was ousted in the 2004 quarterfinals by Deportivo La Coruna, losing the second leg 4-0 after winning 4-1 at home.
"Despite the 4-0 advantage, the English never give up," Allegri said. "So I'm expecting the team to be even better than in the first leg, because we know how difficult it will be."
It will be more difficult to predict the outcomes of the other two last-16 matches this week.
APOEL will be looking to extend its unprecedented Champions League run for a Cypriot side by beating Lyon.
A morale-boosting victory against lowly Ermis on Saturday kept the Cypriot champions in touch with front-runners AEL and Omonia following a bad run of form that had fans grumbling that players were chasing European glory at the expense of the domestic title.
"Now after the game with Ermis that was very important for us to give us the points, we are fully focused on the game with Lyon that certainly will be one of the most important games in the history of APOEL," striker Esteban Solari said after ending a three-month goal drought at the weekend. "We know that if we stick together, this might be a dream that can come true."
By reaching the knockout phase, APOEL with its small €10 million ($13.2million) budget has already achieved what no other Cypriot team has ever done. And APOEL will rely on its tight, disciplined style of play against Lyon and try to exploit the defensive weaknesses of a French side which lost to relegation-threatened Nancy on Saturday.
"We lacked a bit of strength, speed and enthusiasm," Lyon chairman Jean-Michel Aulas said. "When we don't create enough scoring opportunities and make mistakes at the other end, then we lose matches we should be winning.
"It's hugely disappointing, but we have to stand right behind the team ... we need to bounce back mentally."
In Portugal, recent history points to Benfica being able to overturn the 3-2 loss at Zenit, having won 15 of its last 19 home matches in Europe.
But Benfica warmed up for the match with a 3-2 loss at home to leader FC Porto to leave it three points adrift at the top of the Portuguese league. The Russian Premier League only resumed at the weekend, with champion Zenit held to a 2-2 draw by CSKA Moscow.