Pope Francis on Tuesday abruptly canceled his activities for the day because of a flare up in knee pain, the Vatican said.
A statement said his doctors ordered him to rest and that he would not participate in a meeting of an international council of cardinals which advises him on Church matters.
Francis would normally be seated during such a meeting, indicating that the latest flare-up was likely particularly serious.
The 85-year-old pope has had to curtail events in recent weeks because of the pain in his right knee.
Several times over the Easter period, he attended but did not preside at Masses in St. Peter's Basilica. In each case, he delegated an archbishop or cardinal to say the Mass while he sat through the service and also read his homily while seated.
He suspended activities last Friday for medical checks in the Vatican but resumed them over the weekend. On Monday he held six private audiences.
He is scheduled to hold his weekly general audience for the public on Wednesday.