Queen Elizabeth's grandson, Prince Harry and his wife Meghan, say they will not return as working members of the royal family.
The Queen confirmed the couple would not "continue with the responsibilities and duties that come with a life of public service".
A statement from the palace added Prince Harry and Meghan "remain much loved members of the family".
The couple said "service is universal" and offered to continue supporting the organisations they have represented.
The announcment comes in the same week that the Duke of Edinburgh was admitted to hospital.
The duke and duchess said last January they would step back as "senior" royals and work to become financially independent.
The couple, who now live in California, formally stepped down in March, with a plan to review the arrangements after 12 months.
The confirmation means Prince Harry and Meghan will return their honorary military appointments and royal patronages, which will be redistributed to working members of the Royal Family.
Their departure follows conversations between Harry and members of the Royal Family.
A statement from Buckingham Palace said: "The Queen has written confirming that in stepping away from the work of the Royal Family it is not possible to continue with the responsibilities and duties that come with a life of public service.
"While all are saddened by their decision, the Duke and Duchess remain much loved members of the family."
A spokesman for Harry and Meghan said: "As evidenced by their work over the past year, the Duke and Duchess of Sussex remain committed to their duty and service to the UK and around the world, and have offered their continued support to the organisations they have represented regardless of official role."
They added: "We can all live a life of service. Service is universal."
Several of the duke and duchess's former patronages have thanked the couple for their support following the announcement.
The Queen's Commonwealth Trust - which was founded in 2018, with Harry and Meghan appointed president and vice-president respectively - said it was "very lucky" to have had their "keen support and encouragement" in its formative years.
"We are glad that they remain in our circle of supporters," the trust said in a statement.
The Association of Commonwealth Universities said Meghan had been "a passionate advocate for our mission to build a better world through higher education" since she took over the role of patron from the Queen in January 2019.
And the National Theatre, another of Meghan's patronages, said the duchess had "championed" its work with communities and young people across the UK to make theatre accessible to all.
Meanwhile, the Rugby Football League thanked Harry "for his time, care and commitment" in supporting the organisation at all levels - from the children's game to the England teams.
The Rugby Football Union also thanked the duke for his work as patron and vice patron, adding that it had "greatly valued his contribution to promoting and supporting the game".
Invictus games connection remains
However, the Invictus Games Foundation, which runs an international sporting event for injured servicemen and women, said Harry would remain a patron for the organisation.
The duke remained "fully committed" to the games, which he founded, it said in a statement.
"His military service and experience, combined with his genuine compassion and understanding for those who serve their countries, has raised awareness of wounded, injured and sick service personnel and the role they continue to play in society," the statement added.
Smart Works, a charity which helps women with clothes and coaching to get into work, and animal welfare charity Mayhew also said Meghan would remain a private patron.
Which roles will Harry and Meghan give back?
The Duke and Duchess of Sussex's military, Commonwealth and charitable association roles will be handed back to the Queen.
For Harry, those are:
- Captain General, the Royal Marines
- Honorary Air Commandant, RAF Honington
- Commodore-in-Chief, Royal Navy Small Ships and Diving
- President, The Queen's Commonwealth Trust
- Patron, the Rugby Football Union
- Patron, the Rugby Football League
And for Meghan:
- Vice-President, The Queen's Commonwealth Trust
- Patron, the Royal National Theatre
- Patron, the Association of Commonwealth Universities
Prince to remain in hospital
The Duke of Edinburgh, Prince Philip, is likely to remain in hospital until next week, a royal source said, adding that doctors were acting out of an abundance of caution and the duke remains in good spirits.
The Queen's 99-year-old husband was admitted to hospital on Tuesday as a precautionary measure after feeling ill with an ailment that is not related to Covid-19.
"Following consultation with his doctor the Duke of Edinburgh is likely to remain in hospital for observation and rest over the weekend and into next week," the source said.
Both Philip and the 94-year-old queen received their first dose of the Covid-19 vaccine in January.
The Duke was admitted to the private King Edward VII's Hospital in central London after feeling unwell for a short period, Buckingham Palace said on Wednesday.
He spent four nights at the same hospital at the end of 2019 while being treated for a pre-existing condition.
-BBC /Reuters