Also leaving HHS is Caputo's senior advisor, Dr. Paul Alexander. HHS confirmed the departures in a separate statement, noting that Caputo's leave would last 60 days.
Caputo tells ABC News he will continue collecting a paycheck and health insurance from his HHS post while on leave.
The staff departures follow media reports that Caputo and Alexander had pressured the Centers for Disease Control and Prevention to alter scientific reports.
On Sunday, in a private Facebook Live video, Caputo -- a one-time 2016 Trump campaign aide who does not have any prior experience in public health -- accused government scientists of harboring a "resistance unit" at the CDC and predicted there would be shootings on inauguration day. He went on to say he was under siege by the media, adding that his physical health was in question and his "mental health has definitely failed."
"After consultation with President Trump and Secretary Azar, I have decided to take a temporary medical leave of absence to pursue necessary screenings for a lymphatic issue discovered last week," Caputo wrote in a statement released to the press on Wednesday.
"Sometimes we disagree, but we work in unity to defeat the virus and we care for one another," Caputo wrote.
Dr. Robert Redfield, head of CDC, testified before a Senate panel on Wednesday that he was "deeply saddened" to read of what he said were unfounded accusations.
In a Senate Appropriations Committee hearing, Redfield, who did not reference Caputo by name in his testimony, said that there was no truth to the claims.
"I want to make a comment that not only is it not true, it deeply saddens me when I read those comments," Redifield, a Trump appointee, told Sen. Patty Murray, D-Wash.
"As I said in my statement, CDC is made up of thousands of dedicated men and women, highly competent It is the premier public health agency in the world, dedicated 24-7 to use their skills to protect the American public and the world. And it deeply saddened me that those false accusations were made (about) a group of really unbelievably professional people that serve this nation," he added.
Murray said she was deeply concerned about the accusations, as well as recent media reports that political appointees had leaned on the CDC to alter scientific findings.
Redfield denied that the CDC had ever allowed its findings to be influenced by politics.
Adm. Brett Giroir, an HHS official appointed by Trump to coordinate testing efforts, also defended the CDC.
When asked by Murray if Giroir rejects "the unfounded harmful conspiracy theory" that CDC has "deep state ulterior motives," Giroir responded: "I have not seen anything out of CDC ... any of the agencies I've worked with that is anything but people acting in the best interests of the American people. I've currently not seen anything that you described."
At one point, Murray also asked Redfield if he had ever advised Trump to downplay the crisis. In a newly released book by The Washington Post's Bob Woodward called "Rage," Trump says he knew the virus was much more deadly than the flu even though he dismissed those findings in public. The president has since said he didn't want to create a panic.
"No one advised the president to downplay this crisis," Redfield said Wednesday.
When asked if Azar has confidence in Caputo, an HHS spokesperson told ABC News earlier this week in a statement, "Mr. Caputo is a critical, integral part of the president's coronavirus response, leading on public messaging as Americans need public health information to defeat the COVID-19 pandemic."
ABC News' Stephanie Ebbs and Trish Turner contributed to this report.
This report was featured in the Thursday, Sept 17, 2020, episode of “Start Here,” ABC News’ daily news podcast.
"Start Here" offers a straightforward look at the day's top stories in 20 minutes. Listen for free every weekday on Apple Podcasts, Google Podcasts, Spotify, the ABC News app or wherever you get your podcasts.