After four straight Premier League wins using a mix of younger players, United manager Alex Ferguson said he may turn to his more seasoned stars for the opening Group C game in Portugal.
Ferguson is set to recall Darren Fletcher and Michael Carrick to bulk up his midfield, which he expects to be the key battleground in what should be United's toughest group match.
"My team in Lisbon might be different on an issue of experience," Ferguson said. "I think we'll need to have more experience in the game.
"Benfica away from home is the kind of the game you have to respect. ... Benfica are always a handful and we always expect a difficult game. I watched a couple of their games away from home last season and they were absolutely brilliant."
United leads the Premier League on goal difference after scoring 18 goals and conceding only three. Striker Wayne Rooney scored a second straight hat trick in United's 5-0 victory at Bolton on Saturday.
"Rooney is the best British player so far," Benfica coach Jorge Jesus said Tuesday. "But he plays like an Argentinian or Brazilian. He can decide a match in the last third of the field. We will have to pay great attention to him tomorrow."
Ferguson has compared the England international to Brazil great Pele.
"Look at Pele," Ferguson said. "He was a very aggressive attacker as well who could look after himself. So can Rooney. There are similarities that way in strength, speed and determination."
Rooney should again be partnered up front by Mexico striker Javier Hernandez, who marked his first start of the season Saturday with two goals at the Reebok Stadium.
The pair meshed well last season in United's march to the Champions League final, where it lost to Barcelona 3-1 at Wembley Stadium.
United will be without midfielder Tom Cleverley, who sustained a foot injury in that game and will be out for a month. England defender Rio Ferdinand, who has struggled with a series of injury problems, also missed the trip to Lisbon.
Captain Nemanja Vidic (calf), striker Danny Welbeck (hamstring) and Rafael (shoulder) are also out, but defenders Jonny Evans and Patrice Evra are fit again after minor knocks.
Benfica is at full strength for the encounter at the Stadium of Light.
The Portuguese club is in second place in the league after signing a raft of new players. They include striker Nolito from Barcelona, Brazilian midfielder Bruno Cesar from Corinthians, and Argentine defender Ezequiel Garay from Real Madrid.
Belgium international Axel Witsel and Serbian player Nemanja Matic have also helped strengthen the midfield alongside Javi Garcia.
United winger Nani said Benfica is a tougher prospect than it was in the 2005-06 and 2006-07 seasons, when Manchester United won three and lost one Champions League encounter with the Portuguese club.
"Benfica is better than it was in the other years we met," Nani said. "On top of that, it's always hard to play at the Stadium of Light."
In the other group match, Swiss champion FC Basel hosts Romanian club Otelul Galati without suspended midfielder Xherdan Shaqiri.
The 19-year-old Shaqiri, who scored a hat trick for Switzerland in its 3-1 win over Bulgaria last week, is sitting out two games because of a red card in last season's Europa League loss against Spartak Moscow.
Basel coach Thorsten Fink is also missing international midfielders Gilles Yapi of Ivory Coast and Valentin Stocker of Switzerland with long-term knee injuries.
Otelul Galati is making its debut in the competition.
"I am not nervous and I hope my boys will leave their nerves at home," Otelul Galati coach Dorinel Munteanu said. "We are going to Basel to get one point, even more points. It is very hard, but not impossible."