If the Catalans extend their unbeaten run in La Liga to 39 games at the Camp Nou, they will pass the mark set by Real Sociedad in 1980 and take one step closer to a first invincible season.
But while they have been faultless in the league, any celebrations are likely to be tainted by Tuesday's collapse as Barca threw away a 4-1 first leg advantage over Roma and crashed out of the Champions League quarter-finals.
The defeat has been castigated by the Spanish press and Ernesto Valverde's side, still on track for a domestic double, are suddenly finding themselves with questions to answer.
Only Lionel Messi could score a hat-trick one match, then have his form criticised the next, but the Argentinian was out of sorts in Italy and has lacked some of his usual spark in recent weeks.
Blame, however, has been directed less at Messi than the team's ability to cope without him at his blistering best and for this, Valverde has taken most of the flak.
"I hope it will not affect us but this is clearly a blow," Valverde said after the loss in midweek. "We still have important targets ahead and we will see if we can do it."
Barca have earned some room for a sticky patch. They sit 11 points clear of Atletico Madrid in the league and, despite Real's contrasting fortunes in Europe, 15 ahead of Los Blancos.
There is also a certain degree of irony in Zinedine Zidane's side stealing the limelight at the climax of the campaign, which has otherwise been characterised by Barca's relentless consistency.
Beneath Atletico and above Real sit Valencia, whose steady progress under Marcelino has perhaps been under-marked given they are now all but guaranteed to qualify for next season's Champions League. "For some, this is close to a miracle," Marcelino said this week.
While Barca edged both legs in the Copa del Rey earlier this season, Valencia came eight minutes from victory in the reverse league fixture in November, when Rodrigo Moreno's opener was cancelled out by a late Jordi Alba equaliser.
Rodrigo will have a point to prove too this weekend as La Liga's top Spanish scorer aims to secure his place in the national squad for the World Cup. He has six goals in his last five games.
Real may find it too big a wrench to cheer on Barca but any hopes they have of finishing higher than fourth would be well served by a win for the league leaders.
While Barcelona are looking for a lift following their European excursions, Real are set for a reality check as they visit bottom club Malaga on Sunday.
Their last-gasp escape against Juventus on Wednesday overshadowed what was, in truth, a frantic 3-1 defeat at home, only their second loss in 16 games in all competitions.
But there are few better opponents against whom to recover focus than Malaga, who are 15 points adrift of safety and have managed only one win since December.
Cristiano Ronaldo's penalty against Juve was his 25th goal in 14 games but there will be focus too on the reaction of his strike partner Gareth Bale, hauled off at half-time by Zidane, along with Casemiro, when Real were 2-0 down.
"It does not mean that Gareth (Bale) and Casemiro were to blame," Zidane said.
Elsewhere, the Europa League hopefuls go head-to-head as Real Betis in fifth travel to Girona in eighth on Friday, before Sevilla entertain Villarreal on Saturday, in a battle of seventh against sixth.
On Sunday, Atletico host Levante, who may still be riding high following last weekend's win at Las Palmas, which moved them eight points clear of the relegation zone.
Fixtures (all times GMT)
Girona v Real Betis (1900)
Sevilla v Villarreal (1200), Barcelona v Valencia (1515), Las Palmas v Real Sociedad (1730), Leganes v Celta Vigo (1730), Athletic Bilbao v Deportivo La Coruna (1945)
Eibar v Alaves (1100), Atletico Madrid v Levante (1515), Getafe v Espanyol (1730), Malaga v Real Madrid (1945)