The Seleccao travel to London to take on Roy Hodgson's side in their penultimate Euro 2016 warm-up match, with the tournament set to kick off on June 10.
They do so without superstar Ronaldo, who has been given additional time to recuperate following his 120-minute outing in the Champions League final win over Atletico Madrid on Saturday.
"All my players are important. Portugal is not a one-man team. I want to test my whole squad," Santos told ESPN FC.
"When they booked this match we didn't know he would be playing in the Champions League final.
"Ronaldo said he played 4,000 minutes this season, but all my players were tired and they have to rest physically and mentally. I'm not worried about this because we are having good preparation."
The 31-year-old forward is set to join up with the national team ahead of their final warm-up match against Estonia on June 8.
Santos was also complimentary of the quality in the Three Lions squad and talked up the opposition's chances in the much-anticipated tournament.
"I've seen England play. They have talented players and they can win in France. England has big ambition. They are one of the favourites," he said.
"They are one of the strongest teams in the world, both with individual quality and team work. The manager is very clever and it will be a tough match."