John Stones reportedly has a sickness bug and has been confined to his room in order to prevent it spreading among England's squad.
Mail Sport reported on Wednesday morning how the Man City defender hadn't trained due to illness in a worrying sign for the Three Lions.
And, according to Sky Sports, Stones is now a doubt for England's Euro 2024 opener against Serbia on Sunday.
The 30-year-old - who is stuck in his bedroom at England's camp - has 72 caps and has been a mainstay in Southgate's first choice XI.
However, he comes into the tournament off the back of a slightly disappointing campaign with City where he struggled for fitness and gametime.
John Stones has been confined to his room after missing England training through illness
Stones has a sickness bug and is a doubt for England's Euro 2024 opener against Serbia
Stones started just one Premier League match in the final three months of the season and needed training and gametime to get himself up to full fitness after joining up with England.
Unfortunately, with his illness, this may not be possible, meaning his participation against Serbia is in doubt.
Even if he does manage to pull through, he is unlikely to be able to complete 90 minutes due to his lack of match fitness.
Stones is one of five central defenders selected by Southgate for the tournament but he is by far the most important to the success of the side, especially after long-time international partner Harry Maguire was omitted from the squad due to injury.
Stones was an unused substitute in seven of City's last 10 league games and failed to make the squad altogether in another. Despite that patchy involvement at club level, he remains irreplaceable for the national team.
Stones' potential absence provides a major headache for Three Lions boss Gareth Southgate
On Wednesday, England ramped up preparations for their tournament opener against Serbia
Meanwhile, the Three Lions trained for the first time in Germany on Tuesday after arriving at their base at the Weimarer Land Spa and Golf Resort on the outskirts of Blankenhain.
Southgate was handed a double boost with the participation of Luke Shaw and Stones, who was substituted at half-time in the side's final warm-up friendly against Iceland last week after picking up a knock in the early exchanges.
However, Stones' absence from Wednesday's session gives the England boss a headache ahead of Sunday's clash against Serbia, with Ezri Konsa or Lewis Dunk likely to deputise for the City defender if he doesn't make it.