Chelsea defender Reece James has left the England training camp and will not appear in the Three Lions' game against Ukraine at Wembley Stadium tomorrow evening.
The 23-year-old came on in the final few minutes of England's win in Naples against European champions Italy, replacing Bukayo Saka, and did not appear to be suffering any physical discomfort at full time.
However, it has now been confirmed that the full-back will return to his club side "for assessment on an ongoing issue", which will be concerning news for Graham Potter as his side enters a crucial few weeks.
James missed the World Cup as a result of a knee injury which has plagued his campaign and led to him being absent from every game but one between mid-October and the end of January.
Whilst it is unclear exactly what this issue is, the suggestion that he may be set for a spell on the sidelines is no doubt bad news for all of those involved with Chelsea, given his importance to the side.
With the England international in the side, the Blues have an average of 1.78 points per game - no players other than N'Golo Kante (who has only played two matches) and Wesley Fofana have a higher figure than him.
Potter's side are effectively pinning their hopes of a successful season on progression in the Champions League, with hopes of qualifying for Europe's premier competition via the Premier League now non-existent.
They face a monumentally tough task in the form of Real Madrid in the quarter finals, the first leg of which is due to be played in a little over two weeks' time.
'No replacements planned'
Most would agree that having James fit could prove decisive in determining the outcome of the tie, as he has shown in both of the last two seasons how vital he can be against Los Blancos.
Last year he produced a widely-praised defensive performance against Vinicius Jr. at the Bernabeu, whilst the year prior he was part of Thomas Tuchel's team that went all the way to glory, beating Madrid in the last four at that stage.
If they are to come close to repeating that feat this year, they could yet face former head coach Tuchel if he guides Bayern Munich past Manchester City, having recently taken over the German giants following the sacking of Julian Nagelsmann.
If this current injury problem is related to previous knee complications, it will raise questions over James' fitness, as he has found it difficult to get extended runs in the side over the past two years due to various setbacks.
Meanwhile, he will also prove a loss to Southgate as he prepares his side for a second European Championships qualifier against Ukraine, having presided over England's first competitive victory in Italy since 1961.
Southgate has already had other members of his squad withdraw, including another Chelsea star in Mason Mount, who alongside Marcus Rashford and Nick Pope did not turn up to St George's Park due to injury.
Elsewhere, due to his red card on Thursday evening, Manchester United's Luke Shaw will also be unavailable for tomorrow night's fixture, leaving Southgate with 21 of his initial 26-man squad to choose from.
Despite these setbacks though, England have confirmed that "no replacements are planned", meaning Southgate's squad will comprise of those remaining in the camp.
Gareth Southgate is also holding a pre-match press conference today at 3:00 PM GMT which should be a chance to obtain more clarity over the exact nature of Reece James' injury issue which has led to him withdrawing and returning to Cobham.