Barca have already qualified for the knockout round of the competition with two games to spare but are just three points clear of second-placed Inter Milan, who will travel to Tottenham Hotspur on the same night.
PSV's hopes of reaching the knockout round of the competition are over, with the Dutch giants picking up just one point from their four Group B matches to sit bottom of the section. They can still finish in third, however, which would see them continue their European journey for the 2018-19 campaign in the Europa League.
PSV suffered a 4-0 defeat when they travelled to Barcelona in their first group match, and they have only picked up a single point from their three games since. Indeed, sandwiched between 2-1 defeats to Inter and Tottenham was a 2-2 draw against the Premier League club in Eindhoven.
It was always going to be difficult to finish in the top two positions, but a win against Barcelona on Wednesday night would make a Europa League spot a real possibility, although other results would still have to go their way.
Dutch champions for the 24th time last season, PSV will enter this match off the back of 3-0 win over Heerenveen in the league at the weekend. Mark van Bommel's side lead the Eredivisie by five points from second-placed Ajax and have incredibly won all 13 of their league matches this term.
This is the 16th season that PSV have been in the group stages of the Champions League, but they have only reached the knockout round on four occasions, most recently in the 2015-16 season.
PSV have won just four of their 14 home games with Spanish opposition in European football, meanwhile, losing two of their last four. This will actually be the first time that they have welcomed Barcelona to Eindhoven since December 1997, when the pair played out a 2-2 draw in the group stages on that occasion.
There will once again be eyes on the talented Hirving Lozano on Wednesday night. The in-demand forward has scored 13 times in all competitions this season, including one goal in the Champions League.
Recent form: WWLLDL
Recent form (all competitions): WLWLWW
Barcelona's 1-1 draw at Inter earlier this month saw the Spanish champions book their spot in the knockout round of the Champions League, and they currently sit top of Group B on 10 points. Inter are three points behind in second, meaning that a win for Barcelona on Wednesday night would be enough to secure first position in the section.
Barcelona followed their 4-0 win over PSV on matchday one with victories away to Tottenham and at home to Inter, before collecting the point at San Siro last time out. The Catalan outfit are looking to win their section for a record 20th time, and they have actually finished top of their group in each of the last 11 seasons.
Barcelona have reached at least the quarter-finals of the Champions League in each of the last 11 years, but they famously lost to Roma in last season's final eight and have not actually won the competition since 2015. Indeed, the La Liga giants have had to sit back and watch rivals Real Madrid land three straight European crowns.
The Spanish champions have actually won just six of their last 18 away matches in the Champions League, meanwhile, drawing six and losing the other six. They have also lost four of their last 11, and are actually without a victory in their last three in all competitions entering Wednesday's clash in the Netherlands.
Indeed, Barcelona were knocked off top spot in La Liga at the weekend after drawing 1-1 with Atletico Madrid at the Wanda Metropolitano. Ernesto Valverde's side were far from their best in Madrid, but Ousmane Dembele came off the bench to cancel out a header from Diego Costa.
Barcelona have lost just one of their seven European games with PSV, however, and that defeat was back in 1978. The Catalan giants will certainly be confident of sealing first spot in the section ahead of their final Group B game at home to Tottenham, which could be huge for the Premier League club.
Recent form: WLWWWD
Recent form (all competitions): WWWDLD
PSV boss Van Bommel has no fresh injury concerns ahead of the match, meaning that there are not expected to be too many surprises.
Lozano will once again be joined by Luuk de Jong and Steven Bergwijn in the final third of the field. De Jong has 15 goals in all competitions this season, while the latter has six goals and seven assists.
As for Barcelona, Sergi Roberto and Rafinha both picked up injuries during the clash with Atletico at the weekend. The former could be back in a month, but the latter requires knee surgery on a torn ACL.
Philippe Coutinho is closing in on a return from a hamstring injury, but it seems unlikely that the Brazilian will be risked for this match, which could see Dembele come in to start.
There will also be no Luis Suarez for the Spanish champions, with the striker left out of the squad as he requires treatment on a knee problem which could keep him out for two weeks. Suarez's absence could allow Malcom to come into the XI, although Denis Suarez is also an option.
Ivan Rakitic, meanwhile, is back for the Catalan side having missed the clash with Atletico through suspension.
PSV possible starting lineup:
Zoet; Angelino, Schwaab, Viergever, Dumfries; Hendrix, Pereiro, Rosario; Lozano, L De Jong, Bergwijn
Barcelona possible starting lineup:
Ter Stegen; Semedo, Pique, Umtiti, Alba; Rakitic, Busquets, Arthur; Dembele, Messi, Malcom
Head To Head
Wednesday will be the eighth time that PSV and Barcelona have locked horns in European competition. Barcelona have won three of the previous seven, with PSV claiming just one victory.
Aside from earlier this season, the last time that the two teams met was during the 1997-98 competition, and both games finished 2-2.
They also locked horns in both the quarter-finals of the 1995-96 UEFA Cup and semi-finals of the 1977-78 UEFA Cup. Barcelona progressed from the former tie, but the latter saw PSV claim a 4-3 aggregate win.
We say: PSV 1-2 Barcelona
It would not be a surprise to see the points shared in Eindhoven on Wednesday night, but we fancy Barcelona to have enough to claim their fourth Group B win.