Trailing 3-1, Bayer Leverkusen are facing the formidable task of becoming the first club in nearly three decades to overturn a deficit at Barcelona to reach the Champions League quarterfinals.
Barcelona go into Wednesday's game with a number of injury concerns but are comfortably on course to reach the quarterfinals for the fifth straight season.
The European champions have progressed 31 of 33 times when opening a two-leg series with a victory away from home, and not since a 4-1 loss to Metz in 1984 has the Catalan club failed to close it out at the Camp Nou.
Leverkusen have won three straight league matches and are coming off a 2-0 win over Bayern Munich, but the German club hasn't won away from home in Europe in nearly a decade.
Liverpool beat Barcelona 2-1 at the Camp Nou at this stage in 2007 after the English club lost 1-0 at Anfield, but the Spanish champions have won all three last-16 matches under coach Pep Guardiola, beating Bayern Munich, Stuttgart and Arsenal by a combined 11-1.
Barcelona are unbeaten in 13 European home games with 11 victories and the Spanish league club has won nine straight games over German opposition, outscoring their opponents 24-4 on that run.
"Realistically, we don't stand much of a chance. But we want to give Barcelona a game," striker Stefan Kiessling said.
As expected, Guardiola was preaching prudence to his team.
"We are preparing for a Champions League match against a rival that beat Bayern (Munich) 2-0," said the Catalan coach, whose failure to agree to a contract extension continues to distract. "Some may take Leverkusen for granted and underestimate them, but we still have a lot of work to do to get ready for a team with a lot of height that with a corner kick can break open the knockout series."
Barcelona have some injury worries with striker Alexis Sanchez and defender Eric Abidal both missing, while midfielder Thiago Alcantara missed Saturday's 3-1 win over Sporting Gijon with a right leg injury.
Lionel Messi, who leads the competition with seven goals, is expected to return and provide another shirt for Leverkusen's players to squabble over after missing the league win over Sporting with suspension. Leverkusen's players drew the ire of sporting director Rudi Voeller after defenders Michal Kadlec and Manuel Friedrich dueled for Messi's shirt after the first leg loss.
The Germans have a relatively healthy squad with Vedran Corluka a doubt while captain Michael Ballack is missing.