A person familiar with the situation said Armstrong confessed to doping to win the Tour de France, according to a report from AP.
The person spoke on condition of anonymity because the interview is to be broadcast Thursday on Winfrey's network.
Earlier, reports surfaced that the fallen former cycling champion had personally apologised to staff of his Livestrong charity.
"Lance came to the Livestrong Foundation's headquarters today for a private conversation with our staff and offered a sincere and heartfelt apology for the stress they've endured because of him," Livestrong spokeswoman Rae Bazzarre told AFP.
She added that Armstrong - a cancer survivor who founded the charity in 1997 - urged Livestrong staffers "to keep up their great work fighting for people affected by cancer."
Journalists staked out Armstrong's home in Austin earlier Monday ahead of his interview with Winfrey, during which the disgraced cyclist is reportedly planning to admit to doping.
For years he has repeatedly denied taking performance enhancing drugs to win the Tour de France and other big cycling events.