Iran has denied involvement in a drone attack on a US base near Jordan’s border with Syria that killed three US troops.
The US blamed the attack on “radical Iranian-backed militant groups” which also left dozens injured.
US President Biden vowed revenge and said: “We shall respond.”
It is the first time that a strike has killed US troops in the region since Hamas’s 7 October attack on Israel.
There have been other attacks on US bases in the region, but before Sunday there were no fatalities, according to the US military.
The Islamic Resistance in Iraq claimed it was behind that attack.
The umbrella group emerged in late 2023 and is comprised of several Iran-affiliated militias operating in Iraq. It has claimed other attacks against US forces in recent weeks.
In a statement, the group said it had targeted three US bases in Syria – Shaddadi, Rukban and Tanf, as well as an Israeli oil facility in the Mediterranean.
Mr Biden said the US “will hold all those responsible to account at a time and in a manner of our choosing”.
Iran denied US and British accusations that it supported militant groups blamed for the strike.
“These claims are made with specific political goals to reverse the realities of the region,” foreign ministry spokesman Nasser Kanaani said, according to Tehran’s official IRNA news agency.
The White House said Mr Biden was briefed Sunday morning on the attack by US Defence Secretary Lloyd Austin and other officials.
“Jill and I join the families and friends of our fallen – and Americans across the country – in grieving the loss of these warriors in this despicable and wholly unjust attack,” Mr Biden said in a statement.
The names of the servicemen killed and injured have not yet been released as officials work to notify their families.
On a visit to South Carolina, Mr Biden said “we had a tough day last night in the Middle East. We lost three brave souls”.
US officials say at least 34 military personnel were being evaluated for possible traumatic brain injury, and that some of the injured soldiers were medically evacuated from the base for further treatment.
They also say the drone struck the living quarters, which, if confirmed, could explain the high number of casualties.
US Central Command and President Biden said the attack was on a base in northeastern Jordan, near the Syrian border. It was later named by US officials as Tower 22.
In December, US officials said that US bases in Iraq and Syria had been attacked at least 97 times since 17 October.
Last month, the US carried out airstrikes against Iran-affiliated groups after three US servicemembers were injured, one critically, in a drone attack on a base in northern Iraq.
Earlier in January, one retaliatory US strike in Baghdad killed a militia leader accused of being behind attacks on US personnel.
In a pre-recorded interview with ABC News that aired on Sunday morning, Chairman of the Joint Chiefs of Staff Gen CQ Brown said that America’s aim in the region is to “not have the conflict broaden”.
“The goal is to deter them and we don’t want to go down a path of greater escalation that drives to a much broader conflict within the region.”
US and coalition troops are also stationed in the Red Sea after the Iran-backed Houthis began attacking commercial ships in the region. The Yemen-based group says it is targeting vessels in the region in support of Palestinians in Gaza, where Israel is fighting Hamas.
The US military has previously said “these unlawful actions have nothing to do with the conflict in Gaza”.
“The Houthis have fired indiscriminately into the Red Sea, targeting vessels impacting over 40 countries around the world,” US Central Command has said.
Two Navy Seals are presumed dead after they went missing in January during an operation off the coast of Somalia to seize Iranian-made weapons bound for Houthis in Yemen.