Defender George Furbank will miss England’s Premier League opener against South Africa in Johannesburg on Saturday due to appendicitis.
Furbank, 29, was preparing for his first England cap in almost two years before falling ill on Friday night.
England are yet to confirm who will replace him, but Marcus Smith is likely to be in the starting line-up.
Steve Borthwick’s side will take on the world champion Springboks at 16:40 BST at the famous Ellis Park in Johannesburg.
Furbank’s inclusion was one of the main talking points following the team’s announcement on Thursday.
“George Furbank has had so many little setbacks that could really test someone’s character and determination, and he has come through it all,” head coach Steve Borthwick said Thursday.
With that in mind, it’s another desperately unfortunate setback for the 29-year-old, who has suffered arm, calf, knee and concussion injuries since his last England appearance in November 2024.
“This feels like a major blow to England’s attacking prospects and also to the leadership that a Premier-winning captain brings to the field,” said former England midfielder Paul Grayson.
Furbank has impressed at full-back throughout 2024, but has suffered a string of injuries since his last appearance against Japan in November that year.
However, he returned to fine form at the end of the final Premier League season, leading Northampton to the Championship title before a summer move to Harlequins.