"Luka had a scan today and it showed a thigh strain, hence he's been ruled out of the qualifier in Malta because there is not enough time for him to recover," team doctor Boris Nemec said on the Croatian football federation website (www.hns-cff.hr) on Sunday.
Croatia are third in the section and must beat Malta and hope Norway do not beat Italy to finish second and qualify automatically for the tournament in France next year.
They did not say how long the 30-year-old Modric, whose 2014-15 season was disrupted by injury, might be sidelined but Spanish media reported he would almost certainly miss Real's La Liga game at home to Levante on Saturday.
He is also a doubt for the Champions League Group A match at Paris St Germain on Oct. 21.
Modric is the latest Real player to be injured after their France striker Karim Benzema picked up a hamstring problem in a friendly win over Armenia last week. Spanish media said he would be out for around three weeks.
(Additional reporting by Zoran Milosavljevic in Belgrade, writing by Iain Rogers, editing by Ed Osmond)
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