The strike in North Waziristan was the second American drone operation in Pakistan this week.
The attacks come amid American efforts to rebuild its relationship with Pakistan, which in November blocked the passage of U.S. and NATO war supplies to neighboring Afghanistan. The country's parliament has called for an end to the drone strikes, which many here regard as an unacceptable violation of sovereignty.
Up to eight missiles were fired at a house in the Dra Nishtar area of North Waziristan early Saturday, Pakistani intelligence officials said. They didn't give their names because they were not authorized to be named in the media.
Pakistan's foreign office issued a statement condemning the attack, saying it was a violation of sovereignty and international law. It did the same after the strike last Sunday, which was the first since lawmakers demanded they end. Previously, individual attacks rarely drew official complaint.
America is unwilling to stop the drone attacks, saying they have weakened al-Qaida and associated groups in Pakistan's tribal regions, large parts of which are not under the control of the Pakistani state. In the past, Pakistan's intelligence agency has cooperated with the attacks, but the government has not publicly acknowledged this.
U.S and Pakistani intelligence officials are discussing drone operations to see if they can continue in a fashion that is acceptable to Islamabad, American officials say. A central issue is the level of Pakistan involvement in deciding which militant factions are hit.
North Waziristan is a haven for Islamist militants from many parts of the world. Washington regards the region as a key command and control center for insurgents fighting U.S. troops in neighboring Afghanistan. The identities and affiliations of those killed Saturday were not immediately known.
Civilians have also been killed in the drone attacks, but the United States doesn't publicly investigate or apologize for any mistakes it makes. The frequency of the strikes has significantly dropped this year.