Bethell has not played any cricket since July after undergoing surgery to repair cartilage damage in his right knee, and was selected to the tour to Australia but will play any part in the three ODIs or five T20Is.
The news is a significant blow for the 23-year-old as he had been named as Harry Brook's vice-captain in the white-ball formats, with the tour Down Under important preparation ahead of the 2027 World Cup.
"Jacob Bethell has been ruled out of the white-ball tour of Australia following a scan on his right knee," an England spokesperson said on Wednesday.
"Bethell suffered a setback in his return from the injury during a training session in Perth earlier this week. With a busy winter ahead, it was decided that he will return to the UK on Saturday before seeing a specialist."
The injury setback means Bethell will now have to prove his fitness ahead of the three-match Test in South Africa, that begins on 17 December at the Wanderers.
England have included uncapped spinner Liam Patterson-White in their squad for the Test series in South Africa, starting next month, while Jacob Bethell returns after recovering from a knee injury.
England have suffered a blow ahead of their white-ball matches in Australia with the news that fast bowler Josh Tongue has been ruled out of the three-match ODI series with a toe injury.
England white-ball captain Harry Brook wants his team to "hone in on the skills and the lessons" on the current tour of Australia as they build up to next year's ODI World Cup.
England white-ball head coach Brendon McCullum wants his team to play "high-octane" and a "robust" style of cricket as he returns to Australia following the Ashes calamity.
