Messi is his team's leading scorer in Europe with five goals from four Group D games, including two against Panathinaikos - the side Barcelona plays on Wednesday - in a 5-1 win on the opening matchday. He has also scored 10 goals in his last five Primera Liga matches, three of which came in Barca's 8-0 thrashing of Almeria on Saturday.

The Argentina playmaker is sure to be his side's fulcrum in Greece as Barcelona goes in search of a win that will send it through to the last 16, joining already qualified Real Madrid, Chelsea and Bayern Munich.

Defending champion Inter Milan, Tottenham and Manchester United are among the teams also expected to be in the tournament's knockout stage at the conclusion of Matchday 5.

Barcelona has won six matches in a row in the Spanish league, scoring 23 goals in the process, but it has found things tougher in the Champions League.

After a convincing opening victory over Panathinaikos, the three-time winners have won just one of their last three matches - and have leaned heavily on Messi to get them out of trouble in away draws at Rubin Kazan and FC Copenhagen.

Barca, which is a point clear of Copenhagen at the top, is favorite to see off bottom side, which was crushed at the Camp Nou in September.

"The team is playing well and can still improve," said Barcelona coach Pep Guardiola, who will urge his team to focus on Panathinaikos rather than next week's 'clasico' against Real Madrid in La Liga.

"We go to Greece and then we'll think about the game against Madrid," midfielder Andres Iniesta said.

Inter Milan, without a win in four Serie A matches, will seek some respite in the Champions League when it hosts FC Twente in Group A knowing a win will seal progress into the round of 16.

Inter is in the midst of a crisis and club president Massimo Moratti had to reiterate his support for under-pressure coach Rafael Benitez at the weekend.

"We absolutely have to win on Wednesday and keep our heads high," Inter captain Javier Zanetti said. "We will do everything to win." Inter is level on seven points with Tottenham following its 3-1 defeat at White Hart Lane three weeks ago.

Spurs, who will also qualify with a win, are being talked about in the British media as dark horses for the league after its 3-2 come-from-behind win at local rival Arsenal on Saturday. They will be in confident mood heading into Wednesday's match at home to the group's bottom club Werder Bremen.

In Group C, fit-again Wayne Rooney will start for United, which visits Scottish champion Rangers needing a point to secure a top-two finish.

The England striker made his return from an ankle injury when he came off the bench in the second half of the 2-0 win over Wigan on Saturday.

"He's a class player, he's a great teammate and we want Wayne to be at 100 percent now to help the team," United striker Javier Hernandez said of his club colleague.

Second-place Valencia will also advance with a home win over Bursaspor, which hasn't earned a point or scored a goal in four matches so far.

In Wednesday's other matches, Group B play sees the top two, Lyon and Schalke, meet in Gelsenkirchen. Benfica, which is third, is away at Hapoel Tel Aviv needing a win to stay in the hunt for qualification.

On Tuesday, the three teams that have already made it into the last 16 require a point to guarantee top spot in their groups and potentially an easier match in the first knockout round In Group E, Bayern hosts second-place Roma, which is six points adrift of the German side.

Chelsea, which like Bayern is on maximum points after four games, should cruise past bottom side Zilina in Group F to seal top spot and nine-time winner Madrid is five points clear in Group G ahead of its visit to Ajax.

AC Milan will qualify if it beats Auxerre away and third-place Ajax loses at home to the Spanish giants.

Arsenal's 2-1 defeat to Shakhtar Donetsk in Matchday 4 has thrown Group H wide open, with both teams now on nine points. The pressure will be piled on the English side if it loses to Braga, which is three points back in third.

Shakhtar travels to Partizan Belgrade, which hasn't picked up a point in four games.