Jean-Clair Todibo and Moussa Wague will make their Barcelona debuts against Huesca after head coach Ernesto Valverde made sweeping changes to his team.
Todibo, who joined from Toulouse in January, will line up in central defence alongside Jeison Murillo, who is set for his first LaLiga appearance since moving on loan from Valencia.
Wague, 20, will also make his first senior appearance for Barca, whose starting XI shows 10 changes to the team that kicked off the 1-0 Champions League win over Manchester United on Wednesday.
Goalkeeper Marc-Andre ter Stegen is the only player to keep his place, with Samuel Umtiti, Carles Alena, Arturo Vidal, Malcom, Kevin-Prince Boateng and fit-again Ousmane Dembele starting.
There is also a place for Riqui Puig, the midfielder making his maiden appearance in LaLiga.
Barca, who do not have Lionel Messi, Luis Suarez, Gerard Pique, Sergio Busquets or Ivan Rakitic in the squad, are 11 points clear at the top of the table.
They face United in the second leg of their European tie at Camp Nou on Tuesday.