The wing-back appeared to pull up with an injury during Croatia's 2-0 win over Turkey in midweek, clutching his left calf in the 86th minute before being replaced a few minutes later.
Perisic is back with Spurs this morning to join the rest of the squad at Hotspur Way but was unable to join in full training, instead told to work on his fitness away from the main group.
Any injury to Perisic would be a big blow to Spurs, who already have Ryan Sessegnon and Ben Davies sidelined. Emerson Royal, who has briefly played in the position, is also out for the foreseeable.
It leaves Christian Stellini, now acting head coach following Antonio Conte's sacking, with no left-sided defensive options for the tricky trip to Everton on Monday.
Richarlison, who was forced off during Spurs' 3-3 draw at Southampton ahead of the international break, was alongside Perisic and is expected to miss the Goodison Park clash.