"SNL" castmember Alex Moffat took over the role of the former vice president on Saturday night.
However, current Vice President Mike Pence, played by Beck Bennett, was center stage in the show's opening sketch. Bennett's Pence received the coronavirus vaccine on live TV to kick off the show.
"I'm sure all Americans are excited to see me, a guy who let Covid spread everywhere, get one of the first vaccines," he said.
Bennett's Pence told the audience watching at home that the vaccine is "completely safe" and "harmless."
"That's why President Trump refuses to take it or talk about it," he said.
After getting his injection, Bennett's Pence was met on stage by the incoming vice president, Kamala Harris, played by Maya Rudolph.
"How did you even get into the White House?" he asked.
"I won more votes," Rudolph's Harris responded.
Rudolph's Harris then brought out Moffat's Biden, who limped in with a medical boot on his foot before doing a somersault like Willy Wonka.
Benett's Pence pointed out that Biden looked "different, somehow."
"I'm like Colonel Sanders. Every time you see me, I'm a different guy," Moffat's Biden said. "This time next year I'm going to be Mario Lopez."
He then told the American people that they are about to have a "real leader again" and a diverse White House cabinet.
"And I will make sure that Joe never specifies what he means by 'diverse,'" Rudolph's Harris cut in. "That is my Christmas present to you, America."
Before Bennett's Pence could sign off, he was interrupted by Rudy Giuliani, played by Kate McKinnon, who heard that they were giving out "free meds."
Bennett's Pence seemed concerned since hair dye was dripping down Giuliani's face.
"I think all of my bodily fluids are trying to distance themselves from me," McKinnon as Giuliani said.
Bennett's Pence then looked toward the camera and said he hopes America trusts the vaccine now because "you can buy it in the soda fridge at CVS."
"Merry Christmas," he said. "And live from New York... It's Saturday night!"