The Portugal captain missed training on Wednesday and stayed at the gym to do recovery and specific exercises and, with his team already through to the knock-out stages, he could be rested against South Korea even if fit.
"I think it is 50-50 if he plays or not, we'll see," Santos told a news conference on Thursday.
"It will depend on if and how he practices today, if we see he is in good condition ... there is a plan for if he is not available."
Santos confirmed that defender Nuno Mendes will miss the rest of World Cup after the player left the pitch in tears against Uruguay when he sustained a thigh injury.
"Unfortunately he is out but by his will he will stay with us. It was his desire, his club agreed, and he will start his recovery here. His enormous desire to stay with us reflects the state of mind of the whole squad," he said.
"I have complete confidence in all my players, I'm already missing three players, let's see about others," he said.
"Playing every four days is tough, players get tired and are experiencing fatigue. Fatigue leads to stress and stress leads to injuries.
"Winning and finishing top in our group is crucial because we will have an extra day to recover the players in the best way possible."