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Although American media had widely speculated that Armstrong would admit to cheating in the interview, neither Winfrey nor Armstrong would confirm the report, in which the newspaper cited an anonymous source.
"We are not confirming any specific details regarding the interview at this time," a spokesman for Oprah's network OWN told Reuters.
The report did not say which drugs Armstrong admitted to using, and the American's attorney and his spokesman did not immediately respond to requests for comment.
Armstrong, 41, has always vehemently denied using performance-enhancing drugs and had never tested positive to a doping test. But the evidence against him has been overwhelming.
Oprah, on Twitter, offered little more herself other than to say Armstrong came prepared for the interview, which will be broadcast on Thursday.
"Just wrapped with @lancearmstrong More than 2 1/2 hours. He came READY," Winfrey tweeted.
But the television host hinted she would provide some more snippets, confirming she would appear on CBS television on Tuesday morning to talk about the interview.
CBS reported Armstrong had indicated he may be willing to testify against others involved in illegal doping and was in talks about repaying part of the taxpayer money he earned during his career.
The unconfirmed reports about his admissions followed Armstrong's apology to the staff of the cancer foundation he had started over difficulties they may have experienced because of the doping controversy.
"He had a private conversation with the staff, who have done the important work of the foundation for many years," said Livestrong Foundation spokeswoman Katherine McLane.
"It was a very sincere and heartfelt expression of regret over any stress that they've suffered over the course of the last few years as a result of the media attention," she said.
Shortly after, Armstrong joined his legal team to meet with Winfrey for an interview described as "no-holds-barred."
The interview was supposed to take place at Armstrong's Texas home but was switched to a hotel in downtown Austin after news crews camped outside his house before dawn.
SWIFT FALL FROM GRACE
A former cancer survivor who went on to become the greatest cyclist the world has seen, Armstrong's fall from grace has been as swift and spectacular as his rise through the French alps.
Long dogged by accusations he cheated his way to the top, an October report from the U.S. anti-doping body USADA ultimately triggered his rapid slide.
USADA exposed Armstrong as a liar and a cheat, describing him as the ringmaster of the "most sophisticated, professionalized and successful doping program that sport has ever seen," involving anabolic steroids, human growth hormone, blood transfusions and other doping.
Former Armstrong teammates at his U.S. Postal and Discovery Channel outfits, where he won his seven successive Tour titles from 1999 to 2005, testified against him as well as admitting to their own wrongdoing.
The mountain of evidence was overwhelming, and when Armstrong decided not to fight the charges against him, his Tour de France victories were quickly nullified. He was banned from cycling for life.
His sponsors, which had remained loyal to him, began deserting him and he stood down as chairman of Livestrong. Legal issues began to mount.
His former teammate Floyd Landis, a self-confessed cheat, filed a lawsuit against him for defrauding the U.S. government, while the London-based Sunday Times is suing Armstrong to recover about $500,000 it paid him to settle a libel lawsuit.
Armstrong could also be forced to pay back amounts including $7.5 million to SCA Promotions, a Dallas-based company that paid him a bonus for his Tour de France wins.
Throughout it all, Armstrong remained silent, unrepentant and seemingly unconcerned as the cycling world was left reeling by the revelations.
That was until last week, when he announced he had agreed to an interview with Winfrey, prompting speculation he was ready to confess he cheated.