The 37-year-old actress had intended to take at least a year off after her son Rocco - who she has with partner Bobby Cannavale - was born in February 2016, but couldn't turn down the change to appear in HBO drama 'The Immortal Life of Henrietta Lacks' alongside the media mogul, who was also the producer.
She recalled to News.com.au: ''I'd just had a child and I was like, 'I don't really want to go back to work.
''But I read the script and I was like, 'I just...damn it...I can't say no. I want to be in service of this story ... it's an incredible story. I want to work with [writer] George Wolfe. I want to work with Oprah.''
In the film, Rose plays journalist Rebecca Skloot, who befriends Deborah Lacks (Winfrey), a woman seeking the truth about her mother Henrietta's death, and why her parent's cells were used without her family's knowledge for medical research.
And the Australian actress admits it was very intimidating playing a journalist in front of Oprah.
She said: ''It was nerve wracking, you know. She's like the ultimate journalist.
''When you meet someone with such a huge profile it's a strange mix of thinking you know them, and obviously they're a complete stranger, but... there's really not that many people in the world who have her profile.
''She was, to work with though, incredibly professional.
''She had a huge job. There's no vanity in that performance. She was physically transformed, very emotional, very real, with a responsibility to play this woman.''
And Rose felt very lucky that Rebecca was an advisor on the film.
She added: ''I was so lucky. She had so much documented footage behind the scenes, recorded audiotapes of her and Deborah talking on their research trips. Hours and hours of this audio footage, so I was just immersed in that as well, which was great because I could hear them, and hear their relationship unfold a bit.''