Sunday's Mass opened a heavy schedule of Holy Week appointments for the Pontiff, who was treated for a severe bout of bronchitis last week.
Pope Francis presided over Palm Sunday mass in St Peter's Square, his first service after being discharged from the hospital the day before. He was successfully treated for a severe bout of bronchitis.
Thousands of people waved palm and olive branches as the Pope was driven into St. Peter's Square, sitting in the back of a white, open-topped vehicle, before descending and starting the service from beneath an ancient Egyptian obelisk.
In his homily, the Pontiff urged the world to take better care of the poor, the lonely and the infirm.
The pope, 86, was taken to Rome's Gemelli hospital on Wednesday after complaining of breathing difficulties, but recovered quickly following an infusion of antibiotics and returned to his Vatican residence on Saturday.
Palm Sunday marks the start of the Christian Holy Week, leading up to Easter Sunday on April 9 this year. Its numerous events will test the pope's stamina.
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Looking to allay concerns about his health, the Vatican has said he will take part in a full array of Easter events this week, the busiest period in the Roman Catholic Church calendar.
The pontiff, wearing red vestments, spoke with a quiet, but clear voice as he addressed a crowd of more than 30,000 faithful in the weak spring sunshine.
"Today their numbers are legion. Entire peoples are exploited and abandoned; the poor live on our streets and we look the other way; migrants are no longer faces but numbers, prisoners are disowned; people written off as problems," he said.
The pope, who marked the 10th anniversary of his pontificate in March, has long highlighted the plight of the poor and of migrants.
Palm Sunday marks the day that the Bible says Jesus rode into Jerusalem to the cheers of the crowds, the week before Christians believe he rose from the dead following his execution on the Cross.
On Holy Thursday, Francis will celebrate Mass in a prison for juveniles in Rome. It is not yet clear if he will participate in the traditional Good Friday Via Crucis (Way of the Cross) procession around Rome's ancient Colosseum.
The pope, head of the world's nearly 1.4 billion Roman Catholics, will then preside over the Mass on Easter Sunday, the most important day on the Christian liturgical calendar, where he is expected to read his "Urbi et Orbi" (to the city and the world) message.
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