Messi braced to break Muller goal record
The La Liga leaders have already qualified as the top side in Group G and Vilanova rested a number of first-choice regulars for Wednesday's game at the Nou Camp, but not the Argentine World Player of the Year.
INFOGRAPHIC Muller 1972 v Messi 2012
"He rested last week in the King's Cup and we all know he always wants to play," Vilanova told a news conference on Tuesday.
Messi is just one goal short of former Germany and Bayern Munich striker Muller's 40-year-old record with his tally of 84 goals for club and country in 2012.
"We need to be as natural as we can about this," Vilanova added. "Messi has the chance to achieve it and, if we are all waiting expectantly for him to do it, it will make it harder for him.
"He is keen to play and I think he is used to living with all this about him."
Andres Iniesta, Xavi, Javier Mascherano, Pedro, Jordi Alba and Cesc Fabregas were all rested from the squad and replaced with youngsters from the club's youth Academy.
"We have some players just back after injury and others from Barca B and we would like to see how they perform," Vilanova said. "I am sure the motivation will be good. They are professionals. Benfica are still playing to qualify for the last 16."
Benfica are second in the group, level on seven points with Celtic in third, but ahead due to their superior head-to-head record. Celtic host Spartak Moscow.