Trump tweeted in support of Pence saying he is, "doing GREAT" and Harris, calling her a "gaffe machine," a criticism he uses often to attack her running mate Joe Biden.

Biden has also tweeted in support of his running mate during the debate, saying that Harris is "showing the American people why I chose her as my running mate."

In speaking to American leadership, Pence brought up the case of Kayla Mueller, a humanitarian worker from Arizona who was kidnapped by the Islamic State in Syria in 2013 and died in the terror group's custody.

Mueller's parents were in the debate's audience as Pence's guests and appeared last month at the Republican National Convention.

Pence suggested former President Barack Obama and Biden carried blame for Mueller's death, saying they "hesitated for a month" while she was held captive.

Harris, in her response to the topic of American leadership, first addressed Mueller's family.

"First of all, to the Mueller family, I know about your daughter's case and I'm so sorry. I'm so sorry. What happened to her is awful and it should have never happened," Harris said. "And I know Joe feels the same way. And I know that President Obama feels the same way."

In a discussion of foreign policy and the role of American leadership, Harris brought up Trump’s handling of the Iran nuclear deal and criticized the president's “unilateral” approach.

“He's walked away from agreements,” she said. “We were in the Iran nuclear deal with friends, with allies around the country. And because of Donald Trump's unilateral approach to foreign policy, coupled with his isolationism, he pulled us out and has made America less safe.”

“So, Susan, it's about relationships and the thing that has always been part of the strength of our nation, in addition to our great military, has been that we keep our word,” she added. “But Donald Trump doesn't understand that because he doesn't understand what it means to be honest.”

On the issue of jobs, Harris took aim at the Trump administration trade policy with China.

“You lost that trade war. You lost it. What ended up happening is because of a so-called trade war with China, America lost 300,000 manufacturing jobs,” Harris said. “Farmers have experienced bankruptcy because of it. We are in a manufacturing recession because of it.”

Pence responded by criticizing Joe Biden’s record on China, calling him, “a cheerleader for communist China.”

“When Joe Biden was vice president, we lost 200,000 manufacturing jobs and President Obama said they were never coming back,” Pence said.

In response to COVID-19 concerns from Kamala Harris’ team, the Commission on Presidential debates has agreed to add additional safety precautions at the debate.

Vice President Mike Pence and Harris will be seated 12-feet and 3-inches away from each other and from the debate moderator, USA Today Washington Bureau Chief Susan Page. As was the case at the presidential debate, there will be no handshakes between the candidates, and while the Commission said there would also be plexiglass separating Harris, Pence and Page, the Pence campaign has objected to using it.

A senior administration official in Pence’s office told ABC News Tuesday that there had been no formal agreement about the plexiglass and that while Harris and Page could use it, Pence doesn’t want to.

In a statement to ABC News, Pence spokeswoman Katie Miller said, "If Sen. Harris wants to use a fortress around herself, have at it."

Though Harris, Pence and Page will not wear masks on stage, everyone else in the debate hall will be required to wear one. Anyone who takes their mask off will be escorted out, according to the rules.

During the presidential debate in Cleveland, members of the Trump family were seen sitting in the audience without masks, even after being asked to put them on.

Harris and Pence will be tested prior to the debate, according to the Commission, which is a change from the presidential debate when the campaigns were responsible for testing their candidates and traveling parties.

“They’ve got to wear a mask, and if they take their mask off they're gonna be escorted out, and I don't care who they are, they'll be escorted out,” said Frank Fahrenkopf, chairman of the Commission on Presidential Debates, in an interview with ABC News.

The vice president has tested negative each day since Friday, and his White House physician has cleared him from having to quarantine, citing that he is not a “close contact” with anyone who’s tested positive, including Trump.

But Pence was present at the Rose Garden ceremony on Sept. 26 when Trump announced Judge Amy Coney Barrett as his U.S. Supreme Court nominee. Eleven of the attendees have since tested positive for COVID-19. He was also in the Oval Office with Trump the morning of his debate, just days before the president tested positive.

Harris tested negative for COVID-19 Monday after being screened in Salt Lake City, where she has been gearing up for the debate, according to an aide.

-ABC News' Justin Gomez and Averi Harper