On Friday (Saturday NZT), she plans to roll out the legislation that would launch the commission for review.
"The public needs to know the health condition of the president," Pelosi said, later invoking the 25th Amendment, which allows a president's cabinet or Congress to intervene when a president is unable to conduct the duties of the office.
Trump responded swiftly via Twitter.
"Crazy Nancy is the one who should be under observation. They don't call her Crazy for nothing!" the president said.
The president's opponents have discussed invoking the 25th Amendment for some time, but are raising it now, so close to Election Day, as the campaigns are fast turning into a referendum on Trump's handling of the coronavirus pandemic.
More than 210,000 Americans have died and millions more infected by the virus that shows no signs of abating heading into what public health experts warn will be a difficult flu season and winter.
Trump says he "feels great" after being hospitalised and is back at work in the White House. But his doctors have given mixed signals about his diagnosis and treatment. Trump plans to resume campaigning soon.
Congress is not in legislative session, and so any serious consideration of the measure, let alone votes in the House or Senate, is unlikely. But the bill serves as a political tool to stoke questions about Trump's health as his own White House is hit by an outbreak infecting top aides, staff and visitors, including senators.
In a stunning admission, Senate Majority Leader Mitch McConnell - a Republican - said on Thursday he had stopped going to the White House two months ago because he disagreed with its coronavirus protocols. His last visit was on August 6.
Trump abruptly halted talks this week on the new Covid aid package, sending the economy reeling, his GOP allies scrambling and leaving millions of Americans without additional support. Then he immediately reversed course and tried to kick-start talks.
It all came in a head-spinning series of tweets and comments days after he returned to the White House after his hospitalisation with Covid-19.
First, Trump told the Republican leaders in Congress on Tuesday to quit negotiating on an aid package. By Wednesday he was trying to bring everyone back to the table for his priority items - including $US1200 stimulus checks for almost all adult Americans.
Pelosi said on Thursday that Democrats were "still at the table" and her office resumed conversations with top negotiator Treasury Secretary Steven Mnuchin.