Gunmen attacked a US convoy in southeast Nigeria's Anambra State on Tuesday, police and a US official said, killing four people and abducting three others.
Separatists who operate in the region have escalated their attacks in recent years, usually targeting police or government buildings.
"No US citizen was in the convoy," said police spokesman Ikenga Tochukwu.
The gunmen "murdered two of the Police Mobile Force operatives and two staff of the consulate," he said, before setting their vehicle "ablaze".
The attack took place on Tuesday at "3:30pm (14:30 GMT) along Atani, Osamale road" in Ogbaru district, according to the police.
Joint security forces deployed to the scene, said Tochukwu, but the gunmen managed to abduct two police operatives and a driver.
A "rescue/recovery operation" was underway Tuesday evening, he added in his statement.
US National Security Council spokesman John Kirby confirmed the attack during a briefing with reporters in Washington DC.
"A US convoy of vehicles was attacked. What I can tell you is that no US citizens were involved," Kirby said.
The State Department also confirmed the attack.
"U.S. Mission Nigeria personnel are working with Nigerian security services to investigate," a spokesperson said.
"The security of our personnel is always paramount, and we take extensive precautions when organizing trips to the field."
- Outlawed group -
Nigerian officials often blame attacks in the southeast on the outlawed Indigenous People of Biafra movement (IPOB) and its armed wing, the Eastern Security Network.
IPOB has repeatedly denied responsibility for the violence.
The group's leader Nnamdi Kanu is in government custody and faces trial for treason after being detained overseas and brought back to Nigeria.
Separatism is a sensitive issue in Nigeria, where a declaration of an independent Biafra Republic by Igbo army officers in the southeast in 1967 triggered a three-year civil war that left more than one million dead.
Violence in the southeast is just one of the many issues facing president-elect Bola Tinubu, who takes the helm of Africa's most populous nation later this month.
The military is also battling a 14-year-old jihadist insurgency in the northeast, gangs who kidnap and kill in the northwest and central states and piracy in the Gulf of Guinea.
After a brief calm period during February and March elections for the presidency and governorships, attacks have been on the rise in the last few weeks.
Former Anambra State Governor Peter Obi, who ran and lost in the February 25 presidential election, is one of those contesting Tinubu's victory, claiming fraud.
The electoral commission has recognised "glitches" during the vote but has dismissed claims that the process was not free and fair.