Messi scored his club record 21st career hat trick in Barcelona's wild 5-4 victory at Deportivo La Coruna on Saturday, which kept it at the top of the Spanish league alongside Atletico Madrid.
But it's been a decade since the Catalan team last conceded 11 league goals through the first eight rounds, and Celtic will look to exploit the vulnerability at the Camp Nou after coming off a win at Spartak Moscow.
Spartak hosts Benfica in the other group match, and the Portuguese club is already facing a must-win scenario after taking only one point from its opening two games.
Barcelona is hopeful center back Gerard Pique will return from a foot injury with Carles Puyol sidelined and makeshift pair Alex Song and Javier Mascherano unconvincing in a league victory that maintained Barcelona's unbeaten start to the season.
Messi's 15 goals — including a league-high 11 — are the main reason Barcelona is unbeaten through 10 games this season.
"Statistics are just a detail, the important thing is that we keep on winning," Messi said after his 59th goal of the calendar year.
The Argentina forward has already scored 71 goals for club and country in 2012 to leave himself only four shy of matching Pele's record of 75 in a single year in 1959.
"I don't know how you can stop him," said Celtic assistant coach Johan Mjallby, who watched Messi's performance against Deportivo. "He doesn't really play as a recognized striker. We know we can't switch off for a second. We know they are brilliant going forward."
Messi's goals have been aided by Cesc Fabregas, who stepped in to Xavi Hernandez's usual playmaking role with ease in guiding the attack at Deportivo. The former Arsenal captain has turned into a versatile player for coach Tito Vilanova, who has used him in various positions throughout one of the best starts by any Barcelona coach to a season.
"I've always had confidence in my abilities and I'm working really hard," Fabregas said. "I've felt really comfortable in this system since the start of the season."
Celtic is coming off its first Champions League away win in 21 matches but Barcelona is unbeaten at home in 17 in the competition. Celtic is winless in 12 trips to Spain although, the Scottish team has managed two draws at the Camp Nou in three visits.
Benfica, coming off a draw at Celtic and a home loss to Barcelona, traveled to Moscow without midfield trio Pablo Aimar, Nolito and Carlos Martins, who are all injured. Their absence has made room for midfielder Nico Gaitan's return.
Benfica is unbeaten in the Portuguese league this season, but its poor form in Europe has earned it only one point and put the team in danger of slipping further behind in the race to reach the next round.
Spartak is doing even worse after its defense gave up leads in two 3-2 losses in the opening games. Spartak is without forward Pavel Yakovlev (right knee), first-choice goalkeeper Andriy Dykan (shoulder), defender Sergei Parshivlyuk (knee) and Brazilian midfielder Romulo (knee). Backup goalkeeper Sergei Pesyakov is also doubtful because of a foot injury sustained in Saturday's 2-1 loss to Anzi Makhachkala.
"We must beat Benfica to keep alive our chances to continue playing in Europe after the Champions League group stage," Spartak coach Unai Emery said.
Benfica's last victory in Russia came in 1996 at Lokomotiv Moscow.