However, the 33-year-old is poised to return as Euro 2016 champions Portugal step up their World Cup preparations with a warm-up fixture at home to Algeria.
"Most likely Cristiano will be in the starting line-up," Santos told reporters. "We will try to continue with the team's evolution, to analyse the last two matches and try to rectify some things because after this we have the first match against Spain so it's important that the team can learn from these matches and from the last match too."
Of Ronaldo – Portugal's most capped player and record scorer – Santos added: "Any team in the world that has the best player in the world, he must have influence.
"At any team on the world, for any national squad or any club, to have Cristiano Ronaldo will always be very important for his team."
Santos said he still has doubts over his line-up ahead of the showpiece tournament.
"I still have a lot of doubts, there are 23 players but I have a total confidence in all of them," he said. "The match against Spain will be in one week, we are going to see how the training sessions go and how are the players doing.
"I will decide at the right time, that conclusion can't be taken yet with the training sessions to come and any eventual thing that can happen. Of course there's a basis [of players] that is more or less defined but I have full confidence on my 23 players and that's the most important thing."