Mauricio Pochettino appealed to England to treat Harry Kane with care in the two friendlies against Germany and Brazil.
Dele Alli is out of both games with a hamstring strain and Harry Winks is a doubt after coming off at half-time in Sunday’s win over Crystal Palace with a twisted ankle.
Kane, who missed the Old Trafford defeat because of a knee injury, was replaced by the Tottenham manager in the second half at Wembley.
“He was subbed after 75 minutes to protect him after Real Madrid,” Pochettino said. “It was such an emotional game and it is better to avoid a risk.”
The Argentine manager said the Premier League’s top scorer and club talisman should be fit for national service but added: “It’s a difficult situation for everyone.
“The most important thing is the national teams, including England, understand the needs of our players and help them so they will be fit when they return here. The next period of the season is very tough on the players.
“The Premier League is a competition you cannot lose too much in. We try to have a good relationship with all the national teams. We try to explain the situation of everyone and then trust in them they can help our players in a very good way.”
Pochettino revealed Alli first felt a hamstring problem after the Old Trafford defeat. He then played 90 minutes against Real Madrid. It is a very small thing. We hope treatment will go well in the next two weeks and he will be fit to play against Arsenal.”
Winks made his England debut in Lithuania last month and is in line to make his Wembley debut.
The Spurs boss reported: “At the moment it is extremely painful. We must assess him with our medical staff and that of the national team.
"He is so excited to make the national team and I am sure he wants to make it. But it is up to the medical people. What are his chances? I don’t know.”