They may share an illustrious history in the Champions League, with Johan Cruyff being a star for both teams, but this is first meeting between the two sides in a Group H opener.
Lionel Messi concedes that Barcelona faces a tough task progressing from Group H ahead of the Blaugrana's Champions League opener against Ajax.
Wednesday's game at Camp Nou pits together two of European football's most successful teams against one another. Both clubs have won the tournament – whether in its current format or previously as the European Cup – a total of four times apiece.
Lining up along with Barca and Ajax in arguably the toughest group in this season's competition are seven-time European champion Milan and Celtic, which won in 1966-67.
Given the Spanish champion's pedigree in the Champions League, victorious in 2006, 2009 and 2011 and semifinalists in the past two seasons, Gerardo Martino's men will be expected to qualify for the knockout stage, but Messi, who has scored 59 goals in the tournament, feels it is far from a guarantee.
"It's a difficult group, but we knew that would be the case. It's very difficult to win the Champions League – it's already hard from the start," Messi told UEFA.com. "I think the groups are very even, very balanced, so there will be some great games. We hope to play at our best level to be able to qualify.
"There are top-class, historic teams in our group – big names. Teams that we've faced before, so we know them a bit. Maybe not so with Ajax, but we've watched them. It's an exciting group."
Barcelona will be without Jordi Alba for the game after he picked up a hamstring injury in 3-2 win over Sevilla on Saturday, while Carles Puyol (knee), and Ibrahim Afellay (thigh) are unavailable.
Meanwhile, Ajax is likely to be without Siem de Jong, who has only recently recovered from a collapsed lung, but Daley Blind, Ricardo van Rhijn, Thulani Serero and Joel Veltman are all fit to feature.
Barcelona has tasted defeat just twice at home in this calendar year, with Bayern and Real Madrid the only teams to win at Camp Nou, but Ajax defender Niklas Moisander insists the Dutch power will show no fear.
"Barcelona are three, four levels higher than our opponents in the league," Moisander told Nusport. "We are not afraid of a beating, we are going to really try and get something there.
"You should always believe in sensation."