As war escalated across the Middle East and Iran on March 1, Pope Leo XIV, declared that the world is “faced with the possibility of a tragedy of enormous proportions.”

“I address to the parties involved a heartfelt appeal to assume the moral responsibility of halting the spiral of violence before it becomes an irreparable abyss,” the pope said.

Speaking before thousands of Romans and pilgrims in St. Peter’s Square after midday on Sunday, including some from the United States, the American-born pope said, “I follow with profound concern what is happening in the Middle East and Iran in these dramatic hours.” Hours before he spoke, U.S. officials confirmed the killing of Iran’s 86-year-old supreme leader, Ayatollah Ali Khamenei. 

“Stability and peace are not built with mutual threats nor with weapons that sow destruction, pain and death,” Pope Leo said, “but only through a dialogue that is reasonable, authentic and responsible.”

He prayed that “diplomacy may regain its role and promote the good of the peoples who yearn for a peaceful coexistence founded on justice.”

He invited those present and believers worldwide, “let us continue to pray for peace.”

According to media reports shortly before he spoke, Israeli forces were continuing to bomb targets inside Iran. Together with the United States, Israel began what its Prime Minister Benjamin Netanyahu called a “preemptive attack” on Iran on Feb.28. Israeli and U.S. forces have already struck targets in 24 of Iran’s 31 provinces. Iran is a large country the size of Alaska with a largely urbanized population of 93 million people.

President Donald Trump, in a short address on Feb. 28 announcing that the United States was joining Israel in attacking Iran, indicated that he was aiming at regime change in Iran, a nation led by Islamic Shiite clerics since 1979. Iran’s leaders have brutally repressed internal opposition over the years, recently violently suppressing large-scale anti-government protests in January.

Mr. Trump said, “For 47 years, the Iranian regime has chanted Death to America,” adding, “We’re not going to put up with it any longer.”

Iran responded to the joint Israeli-U.S. attack by launching drones and ballistic missiles against Israel—at the closest point the distance between the two countries is around 600 miles. Iran also launched missiles against U.S. military targets in five of the Gulf States and Jordan.

The attack by Israel and the United States on Iran, which began even as negotiations had been continuing between the United States and Iran, sent shock waves across the world. The new conflict has erupted only a few months after a 12-day war in June when Israel and the U.S. had launched an attack on Iran to eliminate its nuclear capability.

What Pope Leo called a “spiral of violence” continued to unfold Sunday as mutual attacks escalated hour by hour throughout the Middle East.

Israel and Iran launched fresh attacks on March 1, with the BBC reporting that Iran’s state-run Islamic Republic News Agency said Tehran has been hit by 60 attacks in 24 hours, leaving 57 people dead—numbers reportedly provided by the Tehran Province Red Crescent Society.

Israel’s military said on X on March 1 that its strikes have killed 40 Iranian commanders, including Abdolrahim Mousavi, the chief of staff of Iran’s armed forces, Abdolrahim Mousavi. Iranian state television confirmed the death.

In the conflict’s opening 24 hours, two people were killed in Tel Aviv as an Iranian missile hit a residential building, while 120 people in Israel were injured from Iran’s counterstrikes, The Jerusalem Post reported.

The Guardian reported Iran’s president, Masoud Pezeshkian, was quoted as having called the killing of Iran’s supreme leader “an open war against Muslims” and having said that Iran “considers bloodshed and revenge against the perpetrators and commanders of this crime as its legitimate duty and right, and will fulfill this great responsibility and duty with all its might.”

Iran’s ally, Russia, condemned Khamenei’s killing, with President Vladimir Putin saying that the “murder” of Khamenei was a “cynical violation of all norms of human morality.”

Mr. Trump took to Truth Social on March 1 warning Iran to not retaliate further.

“Iran just stated that they are going to hit very hard today, harder than they have ever hit before,” Mr. Trump wrote on his social network. He added, “THEY BETTER NOT DO THAT, HOWEVER, BECAUSE IF THEY DO, WE WILL HIT THEM WITH A FORCE THAT HAS NEVER BEEN SEEN BEFORE!”

The U.N. Secretary General, Antonio Guterres, condemned the escalating conflict in a statement to the press. Calling for “an immediate cessation of hostilities and de-escalation,” he added, “failing to do so risks a wider regional conflict with grave consequences for civilians and regional stability.”

“The use of force by the United States and Israel against Iran, and the subsequent retaliation by Iran across the region, undermine international peace and security,” Mr. Guterres said.

In his New Year’s address on Jan. 9 to the ambassadors of the 184 countries that have full diplomatic relations with the Holy See, including the United States, Israel and Iran, Pope Leo warned, “War is back in vogue, and a zeal for war is spreading….The principle established after the Second World War, which prohibited nations from using force to violate the borders of others, has been completely undermined.”

“Peace is no longer sought as a gift and a desirable good in itself,” the pope said. “Instead, peace is sought through weapons as a condition for asserting one’s own dominion. This gravely threatens the rule of law, which is the foundation of all peaceful civil coexistence.”

At that time he called for a return to a diplomacy of sincere negotiations, not the diplomacy of weapons. But, clearly, his words have fallen on deaf ears.

Speaking from the papal study window on the third floor of the Apostolic Palace, Pope Leo also expressed his concern at “the worrying news” of the clashes between Pakistan and Afghanistan and appealed to the two sides “for an urgent return to dialogue.”

He concluded his message today by urging those present and all believers, “Let us pray together that harmony may prevail in all the world’s conflicts.” He reminded them that “only peace, a gift from God, can heal the wounds between peoples.”

Gerard O’Connell is America’s senior Vatican correspondent and author of The Election of Pope Francis: An Inside Story of the Conclave That Changed History. He has been covering the Vatican since 1985.