Messi was already expected to miss out after sustaining a thigh injury against Villarreal in midweek, when he made his first start of the season.
Teenager Fati will be joining the club captain in the treatment room after Barca confirmed he sits out the trip because of a right knee injury.
Messi and Fati being absent means there is a place in Ernesto Valverde's 19-man squad for Carles Perez, who signed a new three-year deal on Friday.
Barcelona has only won six of its past 14 LaLiga away games without Messi, losing six times and drawing twice.
However, its 10 LaLiga wins at Coliseum Alfonso Perez are more than any other side.