The Pope has said he does not know how to explain why some cardinals in the Catholic Church are hesitant to get the Covid-19 jab.
"It's a bit strange because humanity has a history of friendship with vaccines," Francis told reporters during a flight from Slovakia to Italy.
The pontiff, who is vaccinated himself, has previously encouraged people to get jabbed for the "common good".
He said one cardinal had ended up in intensive care with Covid-19.
Francis did not name the man he was referring to, but conservative US Cardinal Raymond Burke, 73, recently spent days on a ventilator in hospital after contracting the virus.
It is unclear whether Cardinal Burke is vaccinated or not, but in the past he has been critical of vaccination.
"Even in the College of Cardinals there are some vaccine negationists," the Pope told reporters aboard the Papal plane. "But one of them, poor thing, has been hospitalised with the virus. These are the ironies of life."
He added that almost everyone at the Vatican was now vaccinated, and that they were "studying how to help" those who were hesitant.
"As children [we were vaccinated] for measles, polio - all the children were vaccinated and no one said anything," he exclaimed.
But the pontiff did recognise that some vaccine debates could increase fears and uncertainty about the jabs, to which he said "we should clarify things and speak calmly".
Some religious leaders, especially in the United States, believe Catholics should be allowed to claim conscientious objection to the Covid-19 vaccines on religious grounds. However Pope Francis has disagreed with this, and said the vaccines were "morally acceptable" and could be used "in good conscience".