Francis, who recently curtailed his speaking engagements because of fatigue related to bouts of bronchitis and influenza, read a long homily during a Holy Thursday "Mass of the Chrism" in St. Peter's Basilica.
Francis urged priests to be compassionate, admit when they have "strayed from the path of holiness" and avoid duplicity, dishonesty and hypocrisy.
During the service, the 87-year-old renewed his vows along with thousands of priests in the basilica and blessed oils that will be used in Church sacraments.
Holy Thursday commemorates the day of Jesus' Last Supper with his apostles the night before he died.
On Thursday afternoon Francis was due to preside at a traditional foot-washing ritual in the women's section of a Rome prison.
Francis is the first pope to hold the foot-washing ceremony outside churches, usually in prisons, homes for the elderly or hospices, continuing a practice he began when he was archbishop of Buenos Aires.
He is also the first pope to include women and non-Christians in the service. The ceremony echoes Jesus' gesture of humility toward his apostles on the night before he died.
On Good Friday, the day Christians commemorate Jesus'crucifixion, Francis is due to preside at a "Passion of the Lord" service in St. Peter's Basilica and then attend a traditional evening Via Crucis (Way of the Cross) procession around at Rome's Colosseum.
He will preside at an Easter Vigil service on Saturday and then on Sunday read his twice-annual "Urbi et Orbi" (to the city and world) message and blessing from the central balcony of St. Peter's to tens of thousands of people in the square below.