Maxwell was to be questioned during a video call to the federal prison camp in Texas where she is serving a 20-year sentence for sex trafficking.
She has come under new scrutiny as lawmakers try to investigate how Epstein, a well-connected financier, was able to sexually abuse underage girls for years.
Maxwell has been seeking to have her conviction overturned, arguing that she was wrongfully convicted.
Ghislaine's deposition comes as lawmakers are searching for anyone who was connected to Epstein and may have facilitated his abuse.
Several Democrats also planned on Monday to look through unredacted versions of the files on Epstein that the US Department of Justice released to comply with a law passed by Congress last year.
The House Oversight Committee subpoenaed her last year, and while her laywers have consistently told lawmakers that she will not answer questions, Republican chairman James Comey insisted on conducting the deposition.
Comer came under pressure to hold the deposition as he pressed for the committee to enforce subpoenas on former president Bill Clinton and former secretary of state Hillary Clinton.
After Comer threatened them with contempt of Congress charges, they both agreed to sit for depositions later this month.
In a post on X after the questioning, Maxwell's legal representative David Markus said his client would be "prepared to speak fully and honestly if granted clemency by President Trump".
Markus also said: "Some may not like what they hear, but the truth matters.
"For example, both President Trump and President Clinton are innocent of any wrongdoing.
"Ms Maxwell alone can explain why, and the public is entitled to that explanation."
Comer told reporters on Monday Maxwell should not be entitled to immunity.
with PA
