Mitchell's departure comes ahead of US President Barack Obama's expected speech laying out his new Middle East strategy and a visit to the White House by Israeli Prime Minister Benjamin Netanyahu on May 20.

There are no imminent plans to announce a replacement for Mitchell, Obama administration officials said, although his staff is expected to remain in place at least temporarily.

Mitchell, 77, a former US senator who helped broker the Northern Ireland peace deal, was one of the first members of Obama's foreign policy team to be announced and has shuttled extensively between Washington and Middle East capitals trying to set up new negotiations.

Direct peace talks resumed briefly last year but broke down over Jewish settlement construction on occupied land.

Faced with a deadlock, the United States in December scrapped efforts to relaunch direct peace talks and Mitchell has not visited the region since then.