The Red and Whites lifted the Eredivisie title in May for the third time in four seasons, and the 24th time overall, but they must now escape a group that also contains Tottenham Hotspur and Inter Milan.
This first assignment looks like being the trickiest of the lot, particularly having lost nine and drawn five of their previous 14 away matches on Spanish soil.
PSV have won seven matches in a row in all competitions, however, and have plenty of momentum on their side for this opening Group B clash.
Here, Sports Mole looks at how Mark van Bommel will set out his side on his return to Catalonia.
Out: Ryan Thomas, Dante Rigo, Maximiliano Romero
Gaston Pereiro also bagged two in the 7-0 destruction of ADO Den Haag last time out, and Luuk de Jong's form has seen him linked with a number of European football's elite clubs - this week's opponents included.
Dutch goalkeeper Jeroen Zoet is another visiting player to have been touted as a target for Barca and will start in goal on Tuesday, likely protected by a back four comprised of Denzel Dumfries, Daniel Schwaab, Nick Viergever and Angelino.
Summer signing Thomas suffered a cruciate knee injury in late August, however, two weeks after signing from Zwolle, and has not been included in the Red and Whites' Champions League squad.