Prince Harry and Meghan Markle are joining US President Joe Biden and stars including Chrissy Teigen, and Ben Affleck for a huge concert which aims to "reunite the world".
The royal couple has called on wealthy countries, philanthropists and the private sector to donate money to ensure all nations have access to vaccines for COVID-19.
In what could be their first joint public appearance since their explosive interview with Oprah Winfrey, the Duke and Duchess of Sussex will deliver a message during Vax Live: The Concert to Reunite the World, which is being held in Los Angeles on 2 May.
Organisers Global Citizen said it would be the "first large-scale music event for a covid-compliant audience of fully-vaccinated frontline healthcare and essential workers", and will be filmed for release in the US and the UK on 8 and 9 May respectively.
Harry and Meghan have joined as campaign chairs, and have been "leading a co-ordinated drive across the private sector to raise critical funds for the vaccine-sharing program COVAX".
In a joint statement, Harry and Meghan said: "Over the past year, our world has experienced pain, loss, and struggle—together. Now we need to recover and heal—together. We can’t leave anybody behind. We will all benefit, we will all be safer, when everyone everywhere has equal access to the vaccine.
"We must pursue equitable vaccine distribution, and in that, restore faith in our common humanity. This mission couldn’t be more critical or important."
Also involved in the campaign is US president Joe Biden, his wife Dr Jill Biden and vice president Kamala Harris.
The line-up includes names like Jimmy Kimmel, Jennifer Lopez, Eddie Vedder, H.E.R., David Letterman and Gayle King and is hosted by Selena Gomez.
Teigen and King are both friends of the Duchess of Sussex.
Vax Live is supported by the World Health Organisation (WHO), European Commission President Ursula von der Leyen, Prime Minister of Italy and G20 Chair Mario Draghi, President Cyril Ramaphosa of South Africa, Prime Minister of Norway Erna Solberg, Prime Minister of Spain Pedro Sanchez, President of France Emmanuel Macron, and the State of California.
Prince Harry, 36, returned to California after a brief trip to Windsor for his grandfather's funeral earlier this month.
Meghan, 39, was unable to attend because she is pregnant with their second child and could not gain medical clearance to go.
Although Harry was seen talking to his brother, Prince William, and his wife Kate, it has been said the brothers did not make any significant progress in their relationship during Harry's stay in the UK.
Harry is next due in the UK in July when he and William will unveil the statue of their mother, Diana.
The brothers have agreed that her wedding dress, which is part of their private collection of her items, will be put on display in Kensington Palace in time for what would have been her 60th birthday.
Watch: Oprah Winfrey was shocked by royal revelations during interview