George Furbank is out of England's Nations Championship opener against South Africa in Johannesburg on Saturday due to appendicitis and could miss the entire summer tour.
The full-back, who was set to make his first England appearance in close to two years, was taken to hospital on Friday evening and has been replaced in the starting XV by Marcus Smith.
Smith's spot on the bench is taken by Henry Slade for a match that kicks off at 4.40pm.
Furbank also appears in doubt for the games against Fiji on July 11 and Argentina on July 18.
The 29-year-old has battled a succession of injuries, including to his calf, arm and knee, since his last England outing in November 2024, but earned a recall after helping Northampton Saints to the Prem Rugby title this summer.
Furbank has recently joined Harlequins.
Speaking earlier this week after Furbank's inclusion, England head coach Steve Borthwick said: "George Furbank has had so many little setbacks that would really test anybody's character and resolve and he has come through it all."
Furbank made his England debut against France in 2020 and has 14 caps to date, scoring three tries.
4.40pm kick-off UK and Ireland time
Starting XV: 15 Marcus Smith, 14 Immanuel Feyi-Waboso, Tommy Freeman, 12 Seb Atkinson, 11 Cadan Murley, 10 Fin Smith, 9 Jack van Poortvliet; 1 Ellis Genge, 2 Jamie George (c), 3 Joe Heyes, 4 Alex Coles, 5 George Martin, 6 Ollie Chessum, 7 Tom Curry, 8 Ben Earl.
Replacements: 16 Luke Cowan-Dickie, 17 Beno Obano, 18 Asher Opoku-Fordjour, 19 Charlie Ewels, 20 Guy Pepper, 21 Henry Pollock, 22 Alex Mitchell, 23 Henry Slade
