But such a confession might lend weight to the lawsuits that could await him.
The interview will air at 9 p.m. ET Thursday on the Oprah Winfrey Network. Winfrey has promised a "no-holds-barred" interview, with no conditions and no payment made to Armstrong.
But the speculations swirled Monday.
"I don't think we're going to get an out-and-out confession," says CNN sports anchor Patrick Snell. "I think we're going to get something like, 'This is what went on during this era of trying to compete at the highest level.'"
Armstrong, 41, has repeatedly and vehemently denied that he used banned performance-enhancing drugs as well as illegal blood transfusions during his cycling career.
Winfrey will ask Armstrong to address the U.S. Anti-Doping Agency's October report, which said there was overwhelming evidence he was directly involved in a sophisticated doping program, a statement from her network said last week.
The International Cycling Union, which chose not to appeal the USADA's lifetime ban, stripped Armstrong of his record seven Tour victories.
The World Anti-Doping Agency also agreed with the sanctions, which means Armstrong may not compete in sports governed by that agency's code.
Before the ban, he was competing in Ironman triathlons and had won two of the five events he had entered.
Since the ban he has entered two non-sanctioned events.
So, why would Armstrong choose to make a confession now?
"I would suspect that he sees this as certainly his best way forward," Snell says. "He would have taken strong legal advice, of course. When you look at the kind of stuff that Oprah's done over the years, it's a chance to get ... heartfelt emotions across."
The New York Times has reported that Armstrong was contemplating publicly admitting he used illegal performance-enhancing drugs. Such an admission might lead toward Armstrong regaining his eligibility.
One of his attorneys denied Armstrong was in discussion with the two anti-doping agencies.
Herman, in a recent e-mail to CNN Sports, did not address whether Armstrong told associates -- as reported by the newspaper -- that he was considering an admission.
But such an admission could open him up to lawsuits, something Armstrong is likely well aware of.
"He is surrounded by the best legal advice, the best legal team," Snell says. "It's very hard for anyone to imagine him going into this without having been fully briefed, made aware of absolutely every scenario."
In the past, Armstrong has argued that he took more than 500 drug tests and never failed.