The 30-year-old joined Sevilla on a free transfer from Real Madrid in August and made 19 appearances in the first half of the season, scoring once and providing three assists.
However, the playmaker has now left Sevilla, with the club confirming his departure on Thursday (AEDT).
Coach Jorge Sampaoli said that a decision on Isco's future was down to the player and the club.
Serie A heavyweight Juventus and Napoli have been linked with a move for Isco, who is also reportedly drawing interest from Premier League sides Aston Villa and Wolves.
Announcing his exit, Sevilla said in a statement: "The club wants to wish Isco all the luck in the world in his new professional challenges."