A 60-year-old woman from southern Dong Thap province died on January 28 and tested positive for the H5N1 virus the following day, provincial medical department director Nguyen Ngoc An told AFP.
It follows the death of a 52-year-old man from the southern Binh Phuoc province on January 18.
Demand for poultry in Vietnam tends to increase at the end of January as families celebrate the Tet lunar new year festival.
The H5N1 virus has caused 649 confirmed flu cases in humans since it re-emerged in 2003, resulting in 385 deaths, according to the World Health Organization (WHO).
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Vietnam has recorded one of the highest fatality rates from bird flu in Southeast Asia.It has claimed 63 lives so far, including one in 2013, according to the WHO.
The WHO figures do not include the two recent deaths in Vietnam.
Neighbouring Cambodia recorded 13 deaths from the virus last year, as it battled its deadliest outbreak since 2003.
Both Hong Kong and China have recently seen a spike in cases of the H7N9 strain of bird flu, although the WHO has said that the rise in cases this year was not surprising due to seasonal factors.