Media reports Tuesday indicated that the Department of Justice had joined other regulators in probing the botched trade, which has caused $2 billion in losses and counting for the nation's largest bank.
"All I can say is we've opened a preliminary investigation," he told the Senate Judiciary Committee.
However, Mueller would not provide any specifics of the investigation, including what potential crimes are being investigated.
The high-profile loss by JPMorgan has driven a fresh round of chatter about Wall Street on Capitol Hill. Proponents of tough financial regulations used the bad trade to bolster their case for further restrictions on the financial sector.
Committees in both the House and Senate have said they plan to hold hearings where the trade will be discussed, and lawmakers will probe regulators on how it could have happened and whether policy needs to be changed in response to the development.
On Wednesday, The New York Times reported that Bruno Iksil, the London trader responsible for the failed investment known as the "London whale," was leaving the bank. His departure comes on the heels of the retirement of Ina Drew, the JPMorgan executive who oversaw its chief investment office.