The infection of a dairy worker in Michigan expands the outbreak of the bird flu although the CDC said the risk to the general public remains low.
The CDC told reporters on a call that it has not seen evidence of human to human transmission of bird flu and that it has tested close to 40 people since March, including the Michigan worker.
A Texas dairy worker was confirmed to be infected in April.
Michigan and Texas are among nine states that have reported bird flu in dairy herds since late March.
Scientists have said they believe the outbreak is more widespread based on US Food and Drug Administration findings of H5N1 particles in about 20 per cent of retail milk samples.
Similar to the Texas case, the patient in Michigan only reported eye symptoms, the CDC said.
The Michigan worker had mild symptoms and recovered, according to the state's Department of Health and Human Services.
The worker had regular exposure to livestock infected with bird flu, Michigan said.
The CDC said "similar additional human cases could be identified" given high levels of the virus in raw milk from infected cows, and the extent of the spread in dairy cows.
Nirav Shah, CDC's principal deputy director, said the agency received the Michigan patient sample on Tuesday and confirmed the positive test result that evening.
The CDC said the investigation is just getting underway, and investigators are looking into whether the worker was wearing or was offered protective equipment.
A nasal swab from the Michigan worker tested negative for influenza in the state but an eye swab from the patient was shipped to CDC and tested positive for the H5N1 virus, the CDC said.
The US Department of Agriculture (USDA) said it believes unpasteurised milk is the primary vector for transmitting the virus among cows although officials do not know exactly how it spreads.
To limit transmission in cattle, the USDA in late April started requiring dairy cows to test negative before being shipped across state lines.
"It's likely that there will be several cases that emanate from exposure to infected cows and their milk amongst farm workers," said Dr Amesh Adalja, an infectious disease expert at the John Hopkins Center for Health security.
"The key thing is to make sure that testing is wide enough to capture them."
