"He has suffered a fibula fracture which needs surgery and (he) will miss approximately three months," Sevilla said in a statement.
Nolito, 32, has only played three league matches this season but scored and provided two assists as Sevilla beat Athletic Bilbao 3-1 on Thursday in the Copa del Rey.
Sevilla visit Athletic in La Liga on Sunday as they bid to cut the gap on leaders Barcelona, who host Eibar, to four points.
(Reporting by Rik Sharma; Editing by Ken Ferris)