The "Once Upon a Time in Hollywood" star launched the second At Home version of the famed late-night comedy sketch show by taking on the role of Fauci, the director of the National Institute of Allergy and Infectious Diseases, for the cold open, during which he tried to clarify numerous confusing statements issued by U.S. President Donald Trump in his regular White House coronavirus task force briefings.
"Good evening, I'm Dr. Anthony Fauci," a suited Pitt began, wearing a pair of glasses and a grey wig while seated behind a desk.
"Now, there's been a lot of misinformation out there about the virus. Yes, the President has taken some liberties with our guidelines. So tonight, I would like to explain what the President was trying to say."
Footage of Trump claiming there would be a vaccine "relatively soon" then aired, before cutting back to Pitt, as Fauci, who mused, "Relatively soon is an interesting phrase. Relative to the entire history of Earth? Sure, the vaccine is going to come real fast (sic)."
He also cleared up a remark the Republican leader had made about how he and his administration had done an "incredible job" handling the pandemic, while declaring COVID-19 would "disappear one day, like a miracle."
"A miracle is great. Who doesn't like miracles?" the actor quipped, adding, "Miracles shouldn't be Plan A."
After throwing a few more jabs at the controversial real estate tycoon and reality star-turned-world leader, Pitt removed his disguise and returned to his normal voice as he shared a message of thanks to essential workers.
"To the real Dr. Fauci, thank you for your calm and your clarity in this unnerving time," he said. "And thank you to the medical workers, first responders, and their families, for being on the frontline."
Pitt's participation in the monologue emerges weeks after Fauci himself joked about having the Oscar winner portray him on a future episode of SNL.
Quizzed about the prospect on CNN recently, the 79 year old replied, "Oh, Brad Pitt, of course."
"SNL" producers debuted their first At Home episode on April 11 when Tom Hanks returned to TV for the first time since beating the coronavirus.
Coldplay's Chris Martin served as the musical guest for that instalment while Miley Cyrus covered Pink Floyd's "Wish You Were Here" for this weekend's show, which also featured cameos by Adam Sandler, Rob Schneider, and Paul Rudd.