The hotel, which is under construction, began to shake just after 0912 (1412 GMT), local media reported. Seconds later, construction crew members inside said they saw parts of the floor give way.
"I see one guy lose his balance and he kind of fell on the concrete and....the concrete started falling," a construction worker said.
At least three people are unaccounted for said Governor John Bel Edwards.
"It is not proper at this point to say that they are trapped because we don't know that, although they may be, which is why this remains a very fluid scene," Bel Edwards said.
It isn't clear what triggered the partial collapse on the higher floors of the hotel.
Compounding concerns for authorities is the fact that a crane positioned near the damaged side of the building could come crashing down.