The statement said one man with confirmed H5N1 died in hospital and his brother, who had not been tested, has also died. The second death is being investigated.
While Pakistan has registered cases of bird flu in poultry this is the first time it has been reported in humans, Federal Health Secretary Khushnood Akhtar Lashari told Reuters.
The first poultry case appeared in early 2006.
Lashari said no more poultry or human cases had been detected in the last two weeks. A World Health Organisation (WHO) team will arrive in Pakistan in the next few days.
It has so far appeared difficult for humans to contract H5N1, which is mainly an animal disease. But experts fear the strain could spark a global pandemic and kill millions if it mutates to spread more easily.
The Geneva-based WHO said it was aware of eight suspected human cases of H5N1 bird flu in Pakistan's Peshawar region.
"These cases were detected following a series of culling operations in response to outbreaks of H5N1 in poultry. One of the cases has now recovered and a further two suspected cases have since died," the United Nations agency said in a statement on its Web site www.who.int.
WHO spokesman Gregory Hartl said the first known person infected with H5N1 in Pakistan was a man who had worked as a poultry culler, who died as a result of the virus.
Two of his brothers had also fallen ill, one of whom subsequently died. It has not been confirmed whether the second death occurred as a result of the man caring for his brother or from exposure to infected birds kept in their home, Hartl said.
"The details are not 100 percent clear ... The virus has not been characterized yet," Hartl said, referring to analysis on whether the bird flu strain had mutated. "There are several cases within one family. We don't know how the family members contracted the virus."
The Pakistani cases bring to nearly 350 the number of people worldwide who are known to have contracted the H5N1 virus, which has killed more than 200 people since 2003.
Indonesia has had the heaviest toll, with 115 human cases including 92 deaths, followed by Vietnam with 100 cases and 46 deaths, according to WHO figures.
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