The government says the man had West Nile virus neurological syndrome, a rare but more serious condition caused by the virus.
The man was a resident of the Interlake-Eastern Health region and the government says he was exposed to the virus during the first half of August.
No other details will be released, says the government, to protect the man's health information.
Human cases of West Nile virus — which is spread through mosquitoes —were first reported in Manitoba in 2003.
The government says this is first death reported since January 2008 and the eighth death since the province began collecting this information.
The province previously reported this year's first human case of West Nile virus infection on Aug. 22, involving a woman in her 40s who experienced mild symptoms.