The pontiff decried what he called a "sharp intensification" of the war in Ukraine, telling pilgrims at his weekly audience at the Vatican that he wanted to express closeness to civilians killed in recent attacks.
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"I am following with concern the war in Ukraine," Leo XIV, the first U.S.-born pope, said. "War does not solve problems, but aggravates them. It does not build security, but multiplies suffering and hatred".
"Where missiles and drones fall, hopes also fall, homes and places of worship are destroyed, and innocent lives are shattered."
Pope Leo XIV previously discussed Russia's escalating attacks with Ukrainian President Volodymyr Zelensky during a phone call in April focused on peace talks and Kyiv's proposal for a ceasefire and also offered to host negotiations at the Vatican.
Last month, the Pope was also involved in a war of words with American President Donald Trump. Mr Trump, in a rant that was posted on social media, claimed the Pope was "weak on crime, and terrible for foreign policy". His full message read: "I don’t want a Pope who thinks it’s OK for Iran to have a nuclear weapon. I don’t want a Pope who thinks it’s terrible that America attacked Venezuela, a country that was sending massive amounts of drugs into the United States and, even worse, emptying their prisons, including murderers, drug dealers, and killers, into our country."
After Mr Trump's message, speaking during an evening peace vigil at St Peter’s Basilica in Vatican City on Saturday, the Pope issued a direct appeal to world leaders to return to negotiations in Iran. "Enough of the idolatry of self and money! Enough of the display of power! Enough of war! True strength is shown in serving life," he said.
Although the Iran-US conflict was not specifically mentioned, the remarks came as a round of negotiations between the two nations took place in Pakistan at the time.
Pope Leo also warned against what he called "that delusion of omnipotence that surrounds us and is becoming increasingly unpredictable and aggressive".
Replying to Mr Trump, Pope Leo, who at the time was starting a visit to Africa, said: "I am not afraid of the Trump administration. I speak of the Gospel and therefore I will continue to speak out loudly against the war. I have no intention of entering into a debate with him."