The Spain international has not played since the end of last season when he was a key man in the Catalans' 3-1 demolition of Manchester United in the Champions League final at Wembley.
He subsequently underwent a knee operation a month later which forced him to miss the pre-season tour of the United States.
He is likely to slot straight back into his customary central defensive role with Pep Guardiola set to revert to a four-man backline after experimenting in the 5-0 mauling of Villarreal on August 29.
The defeat of the Yellow Submarine was remarkable for the fact Guardiola named just one recognised defender in his starting XI - France international Eric Abidal - with midfielders Javier Mascherano and Seydou Keita dropping back in a 3-4-3 formation.
But with Puyol back from injury, along with left-backs Adriano and Maxwell, and right-back Daniel Alves available again after suspension, Barca's starting XI is likely to have a more familiar look about it.
Guardiola will be relieved to have a shored-up defence as his men attempt to make up for a 2-1 defeat at the Anoeta last season - the only defeat on their travels in the Primera Division.
On that evening in April, French winger Antoine Griezmann was instrumental in firing the Basque side to a victory which went a long way to securing their top flight survival.
Griezmann comes into the fixture this season under a cloud, however, after granting an interview in the summer in which he declared his desire to leave the club to play alongside "big players" at Atletico Madrid.
The deal subsequently collapsed, leaving Griezmann with relationships to rebuild, not least with the supporters.
He told the Diario Vasco: "I want to apologise again, turn the page and say that I regret what happened.
"On the pitch I will show my commitment to Real."
As for his reception from the Anoeta crowd, he added: "I prefer not to think about it. We'll see what happens.
"If they whistle again, I understand, but mostly I want them to encourage my team-mates."
Griezmann missed the season-opening 2-1 win at Sporting Gijon - a result he believes offers encouragement for the rest of the season.
"That victory means we have a good squad and we can do something this season in the league," he said.
"I know I have to work hard to earn a place in the team but I also know the competition will be good for me and everyone else."