Ernesto Valverde's side lead the Primera Division by four points from Marcelino's men after 12 rounds of matches, with Real Madrid and Atletico 10 behind the Catalan club.
Here, Goal takes a look at everything you need to know ahead of Sunday's top-of-the-table clash...
Ousmane Dembele is still sidelined with a thigh injury, but the French forward could be back earlier than expected and may feature in the Clasico against Real Madrid before Christmas.
Sergi Roberto, Andre Gomes and Rafinha are all still sidelined, while Javier Mascherano also misses out after picking up an injury on international duty with Argentina earlier this month.
Gerard Pique is suspended after picking up a fifth yellow card of the season in La Liga in the 3-0 win away to Leganes last weekend.
BARCELONA POTENTIAL STARTING LINE-UP
Messi will return to the starting line-up for Barcelona on Sunday after surprisingly starting on the bench in Turin on Wednesday.
The Argentine is set to feature in a deeper role, with strikers Luis Suarez and Paco Alcacer paired together further forward.
However, the biggest dilemma for coach Valverde comes in central defence, where Pique is out through suspension and Mascherano sidelined. In their absence, Thomas Vermaelen is in line for a rare start.
VALENCIA TEAM NEWS
Valencia have been a revelation in La Liga this season, winning nine and drawing three of their 12 fixtures so far.
That impressive run means it is second versus first at Mestalla and Marcelino's men have won five out of six at home in the Primera Division so far this term, scoring 16 and conceding only twice.
Marcelino will have to watch from the stands after he was sent off in the win at Espanyol last Sunday, while central defenders Jeison Murillo and Javi Jimenez both miss out through injury.
Simone Zaza, Carlos Soler and Goncalo Guedes should all return to the side after they were rested at Cornella.
BEST OPTA MATCH FACTS
Valencia have won only two of their last 20 league games against Barcelona (losing 13 of those), and both were as visitors (3-2 in February 2014 and 2-1 in April 2016).
At home, Valencia are winless in their last 10 league games versus the Blaugrana (with five draws and five losses in those games). Their last victory in the competition against Barca at Mestalla was in February 2007 under Quique Sanchez Flores (2-1).
Valencia have won eight consecutive games in La Liga, their best winning streak in the competition.
Lionel Messi has had a hand in 26 of Barcelona’s last 33 goals against Valencia in La Liga (with 20 scored and six assisted).
Santi Mina has already scored five league goals in his 12 appearances this season, having hit just six in his previous 29 league games. Mina, with two, is the only Valencia player to have netted more than one goal against Barca.
TV COVERAGE & KICK-OFF TIME
Valencia versus Barcelona kicks off at 20:45 local time at Mestalla on Sunday and will be broadcast live from 19:40 UK time on Sky Sports Football.