The Spanish champions sit a point behind surprise early pace-setters Villarreal after six fixtures this season.
Luis Enrique’s side suffered a significant blow in their quest to retain the title last week as Messi was ruled out for up to two months with a knee injury.
Barca responded to the absence of their talisman in midweek, coming from behind to overcome Bayer Leverkusen 2-1 in Tuesday’s Champions League clash.
The victory, though, belied a difficult evening for the hosts, who were subjected to booing from the demanding Camp Nou faithful after Kyriakos Papadopoulos gave the German side an early lead.
And those displays of dissatisfaction certainly irked Luis Enrique.
“The team deserves more credit,” he told TV3 after seeing late goals from Sergi Roberto and Luis Suarez earn Barca the spoils. “You should support the team before, not only when it’s going well.”
This is perhaps an ideal time, then, for Barca to head to ground where they have not tasted defeat in the league since March 2007.
They will make the journey this time with considerably depleted ranks, however.
As well as being without Messi, Barca are likely to be unable to call upon midfield maestro Andres Iniesta after he was withdrawn due to a hamstring complaint in midweek.
The club have not revealed his prognosis as yet, although some reports are suggesting he could be missing for a month.
Thomas Vermaelen and Rafinha remain sidelined with calf and cruciate knee ligament injuries respectively.
The good news, however, is that Claudio Bravo is fit following a calf problem and expected to replace Marc-Andre ter Stegen in goal.
Should he reclaim his place, Bravo will be tasked with keeping out a Sevilla side smarting from a poor start to the campaign.
The Europa League holders have managed just one win in their first six league outings, although that came last time out when Yevhen Konoplyanka’s late goal secured a 3-2 success over Rayo Vallecano.
Any momentum gleaned from that win was undermined on Wednesday as Sevilla slipped to a 2-0 Champions League loss to Juventus.
However, they will have Vitolo and Fernando Llorente back in their ranks. The duo missed last Saturday’s win over Rayo and were rested against Juve to ensure full fitness for Barca’s trip.
The last meeting between the sides was a nine-goal thriller, with the now-departed Pedro grabbing the decisive extra-time goal in Barca’s 5-4 UEFA Super Cup victory in August.