The influential Spain international last only 10 minutes of Saturday's 4-0 hammering of the Liga leaders at Vicente Calderon before he was replaced by Saul, who scored the second goal just eight minutes after coming on.
Rising star Saul could now get a run in Diego Simeone's side, as Atleti have revealed that Koke sustained a grade two tear of his left hamstring.
The Spanish champions did not state how long the 23-year-old will be sidelined, but he could be out for at least a month.
Real also suffered an injury blow in Saturday's rout, with the European champions stating on Monday that Germany international Sami Khedira has also damaged his left hamstring.
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