The Spanish team leads the league after winning all four of its games and, despite losing the Spanish Super Cup to Real Madrid, has opened up an eight-point lead over its biggest domestic rival.
Vilanova is no stranger to Barcelona's recent success in the competition, having been assistant coach when the Catalan club won the competition in 2008 and 2011. But the relative ease in which he has been able to take over a team led by Lionel Messi, Xavi Hernandez and Andres Iniesta has still been somewhat surprising.
"I don't feel any extra pressure because of it because I've already been here four times before," Vilanova said on Tuesday. "I put the pressure on myself, it doesn't come from the outside."
Vilanova will be without Iniesta and Carles Puyol (leg injuries) and Jordi Alba (flu), while Alexis Sanchez has made the squad but without medical clearance to play.
Barcelona hasn't been beaten in 16 matches at the Camp Nou. Not since a 2-1 loss to another Russian club, Rubin Kazan, in October 2009.
David Villa continues to put his leg injury behind him as the Barcelona striker scored for the second time this season in a 4-1 win at Getafe, where Messi came on as a substitute to take his season tally to eight goals with a pair of scores.
Spartak coach Unai Emery knows his rival well after having coached for Valencia and Almeria in Spain before joining the Russian club. But the Spanish coach never managed to secure a victory in his 12 matches against Barcelona.
"There's no use in looking back, not when you win or you lose," Vilanova said a day after celebrating his 44th birthday. "In the Champions League we have to be attentive right from the start, our experience tells us so as we've had a tough time in the group phase before."
Spartak returns to the competition after a six-year absence led by the arrival of a number of midfielders, including Romulo of Brazil, Kim Kallstrom of Sweden and Spanish playmaker Jose Manuel Jurado. It is struggling domestically as a 2-2 draw at Kuban Krasnodar on Saturday left it with one point from its last three league matches.
Celtic returns to the competition for the first time in four seasons to play Portuguese club Benfica in the other Group G match on Wednesday.
But the Scottish champions' form has been woeful this season, sitting in fifth place after five games. Rangers was demoted to Scotland's bottom tier because of financial irregularities.
Celtic was beaten by St. Johnstone 2-1 on Saturday.
"I think some players are not concentrating on what they should be doing and thinking about the Champions League," Celtic coach Neil Lennon said. "They need to buck up their ideas.
"We need to get back on the horse very quickly," he added. "There'll be a full house and I'm expecting a big performance from them."
Benfica defender Luisao travelled to Glasgow despite the threat of a FIFA ban that could see him miss the match at Celtic Park.
Last week, the Brazilian was suspended for two months by the Portuguese Football Federation after clashing with a referee during a preseason friendly in Germany. FIFA has not yet said whether the suspension will be valid outside Portugal, which could keep him out of Benfica's first four Champions League matches.
The Lisbon club will be without midfield playmaker Carlos Martins, out with a thigh injury, and suspended right back Maxi Pereira.
Two-time European champion Benfica reached the quarterfinals last season but sold Axel Witsel and Javi Garcia in the off-season.