In an in-depth interview with InStyle magazine given three weeks before her famed Golden Globes speech, the 63-year-old talk show host said the presidency was "not something that interests me".
"I actually saw a mug the other day," she told the publication, when asked about the twitter trend #Oprah2020. I thought it was a cute mug. All you need is a mug and some campaign literature and a T-shirt. I've always felt very secure and confident with myself in knowing what I could do and what I could not. And so it's not something that interests me. I don't have the DNA for it."
Comment: She also doesn't have any credentials for the job. All she has is support from the Left and an ability to virtue signal in public.
Shortly before the interview, Oprah's house had been surrounded by the wildfires which devastated large parts of California.
Also this month, she received the Cecil B DeMille Award at the Globes, and gave an emotional speech tackling social issues from racism to sexism.
Rumours re-kindled online that Winfrey should and could run for president in 2020.
"Gayle (TV presenter Gayle King) - who knows me as well as I know myself practically - has been calling me regularly and texting me things, like a woman in the airport saying: 'When's Oprah going to run?'," she told InStyle magazine.
"I met with someone the other day who said that they would help me with a campaign. That's not for me."
But close friends said private discussions had been ongoing for months, adding that she was "actively thinking" about running.
Members of Winfrey's inner circle, including her long-time partner Stedman Graham and Gayle King, have hinted she might consider a bid.
"It's up to the people," Mr Graham told the Los Angeles Times when asked about a possible campaign. "She would absolutely do it."
Donald Trump said he did not think the actress and talk show host would run. But he added: "Yeah, I'll beat Oprah. Oprah would be a lot of fun.
Comment: Previously: