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Giannakopoulos lasted 49 minutes of the Group A contest but was unable to impose himself on the game which was controlled by Spain for the majority of the night.
It is the second time that the former Olympiakos man has been withdrawn, he left the field of play in the second half of his country's opening European Championship game against hosts Portugal.
Greece lead their respective group on goal difference and no matter what happens in their final group fixture they will qualify for the next stage of the competition.