According to CBS, the start of the interview will be between only Winfrey and Meghan, with Prince Harry joining later.
The channel has said that the Duchess will be interviewed about a range of subjects, including “stepping into life as a royal, marriage, motherhood” and “how she is handling life under intense public pressure”.
Meanwhile, Harry will later join her to discuss their move to the US and their plans for the future.
Ahead of the highly anticipated interview, we’ve rounded up a few key talking points we suspect might come up.
Her relationship with the British media
One subject that many suspect Meghan will be asked about is her relationship with the British media.
Last week, the Duchess won a High Court privacy claim against the Mail on Sunday over the publication of a “personal and private” handwritten letter to her estranged father, Thomas Markle, in February 2019.
Both Meghan and Harry have spoken publicly about their relationship with the press.
In 2019, Meghan said that her British friends warned her not to marry Prince Harry as the tabloids in Britain would “destroy” her life.
The Duchess made the comments in the ITV documentary Harry and Meghan: An African Journey, which followed the couple on their royal tour of southern Africa.
“When I first met my now-husband my friends were really happy because I was so happy, but my British friends said to me: ‘I’m sure he’s great but you shouldn’t do it because the British tabloids will destroy your life’,” Meghan said.
Married life and motherhood
According to CBS, Meghan will speak to Oprah in more detail about her marriage and motherhood.
In addition to discussing her son Archie Harrison Mountbatten Windsor, and the fact that she and Harry are now expecting their second child, it’s likely that Meghan will address her miscarriage last year.
In November, the Duchess revealed she had suffered a miscarriage over the summer. Writing in The New York Times, Meghan recalled a morning in July changing Archie’s nappy when she felt a “sharp cramp”.
“I dropped to the floor with him in my arms, humming a lullaby to keep us both calm, the cheerful tune a stark contrast to my sense that something was not right,” the Duchess wrote.
“I knew, as I clutched my firstborn child, that I was losing my second.”
Meghan might also be asked about her first marriage to American film producer Trevor Engelson, whom she divorced in 2013 after two years of marriage.
One subject that Meghan frequently speaks about publicly is anti-racism. It’s likely this will be addressed during her interview with Oprah.
But racism is a subject Meghan has long-addressed even before she became a part of the royal family.
In 2017, she wrote an essay for her former lifestyle blog, The Tig, about the racism she and her family have encountered.
She recounted her black grandfather telling her about being forced to eat in the car park at a KFC because of the colour of his skin.
“That story still haunts me,” she wrote. “It reminds me of how young our country is. How far we’ve come and how far we still have to come.”
Before that, in 2015, the former Suits star wrote a piece for Elle Magazine in which she described an incident when her mother, Doria Ragland, was verbally abused by another driver in LA, who called her “the ‘N’ word”.
Prince Harry has also spoken at length about racism and released a strongly worded statement in 2016 shortly after it was revealed that he and Meghan were dating.
In the piece, Harry referenced the “racial undertones of comment pieces” that emerged in the press at the time and the “outright sexism and racism of social media trolls” with regards to comments made about his then-girlfriend.
Her childhood and relationship with her father
Meghan might also be asked about her upbringing in the interview, something that she has seldom discussed publicly.
Prior to becoming an actor, Meghan interned at the American embassy in Buenos Aires and is said to have once considered a political career.
While it is unlikely that Meghan will speak at length about her father, Thomas Markle, given the recent court case, she might reference his role in her upbringing.
Mr Markle is said to be making a documentary about his life with Meghan, it has been claimed.
In January, Markle toldThe Sun: “It begins with my life, my family, my love of theatre and television and how I got there.
“Then my life with Meghan, growing up, her school days until she went off to college, and when her career began.”
Social media trolling
Meghan has spoken at length about being trolled on social media since becoming part of the royal family.
Last year, she said that she was “the most trolled person in the entire world in 2019” in a podcast recorded for World Mental Health Day.
Meghan made the remark on an episode of the podcast Teenager Therapy while discussing online abuse.
“I can speak personally too because I’m told that in 2019 I was the most trolled person in the entire world – male or female,” she said.
“Now eight months of that, I wasn’t even visible. I was on maternity leave or with a baby. But what was able to just be manufactured and churned out. It’s almost unsurvivable.”
CBS has said that the couple will discuss their plans for the future in the interview.
Last year, the couple signed several high-profile deals indicating what their next projects will be.
This included an exclusive podcast deal with Spotify that will see them host and produce podcasts with their newly formed Archewell Audio production company.
In September, it was also revealed that the couple signed a deal with Netflix to make documentaries, docu-series, feature films, scripted shows and children’s programming.
Royal fans are hopeful that Meghan and Harry will share more details for what these deals will mean for them and the content they plan to produce in the future.