England centre Manu Tuilagi will miss this summer's tour of Australia to have surgery on a knee problem.
The 31-year-old has played only six games for England since 2019's Rugby World Cup final as injury continues to dog his career.
Club side Sale said they and England had decided "a summer of rest and a full pre-season is the best course of action" for Tuilagi.
His absence poses a continuing problem for England head coach Eddie Jones.
Jones is believed to have identified a lack of midfield power and pace out wide as key factors in an underwhelming Six Nations that featured three defeats in five games.
England finished the Six Nations with Henry Slade and Joe Marchant as their first-choice 12-13 combination, with Tuilagi absent for the tournament after picking up an injury in the autumn win over South Africa.
However Slade also appears to be out of July's tour after he announced on social media on Wednesday that he has had an operation on a long-standing shoulder injury.
Northampton's Fraser Dingwall and London Irish's Will Joseph were uncapped centre options included in last month's training squad for the three-Test series against the Wallabies.
Tuilagi has suffered with a string of injuries throughout his career.
He had not started a match for England for more than four and a half years, before hitting a run of form and fitness in the 2019 Six Nations that cemented his place as a key part of Jones' set-up for the year's World Cup campaign.