Declan Rice has withdrawn from the England squad due to illness.
The West Ham midfielder is the latest member of Gareth Southgate's squad to pull out of the upcoming World Cup qualifiers against Albania and San Marino.
Southampton midfielder James Ward-Prowse and Marcus Rashford of Manchester United had already returned to their clubs.
"Declan Rice has withdrawn from the England squad," the Football Association confirmed in a statement on Wednesday evening.
"Having been unable to train due to illness since reporting to St. George's Park, the midfielder has returned to West Ham United and will play no part in the forthcoming FIFA World Cup qualifiers.
"No additions to the squad are planned at this moment in time. Mason Mount and Luke Shaw are still yet to link up with the group and continue to be assessed following dental surgery and concussion respectively."
Rice has enjoyed a strong start to the season with the Hammers, who sit third in the Premier League having beaten Liverpool last weekend.
Southgate may have lost three players but so far only Arsenal attacking midfielder Emile Smith Rowe has been added as a replacement, being promoted from the under-21 squad for his first senior call-up.
Follow the Republic of Ireland v Portugal via our liveblog on RTÉ.ie/sport and the RTÉ News app, watch live on RTÉ 2 and the RTÉ Player, or listen to live radio commentary on 2fm's Game On.
We need your consent to load this SoundCloud contentWe use SoundCloud to manage extra content that can set cookies on your device and collect data about your activity. Please review their details and accept them to load the content.Manage Preferences