Argentina striker Higuain is suffering from back pain and Germany midfielder Khedira has a strained right hamstring after both were substituted during Real's 5-1 victory at home to Athletic Bilbao in La Liga on Saturday.
Jose Mourinho's unbeaten side have already assured themselves of a place in the last 16 of the competition and travel to Amsterdam on Tuesday needing only a point to secure first place in Group G.
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