Culex nigripalpus has been found to occur in the following countries: Anguilla, Bahamas, Barbados, Belize, Brazil, Colombia, Costa Rica, Cuba, Dominica, Dominican Republic, Ecuador, El Salvador, French Guiana, Grenada, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico, Montserrat, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago, United States, Venezuela, Virgin Islands. In the United States, it is found from Texas to North Carolina in warm, humid coastal habitats and in the Mississippi River basin as far north as Kentucky.
Culex nigripalpus is a principle disease vector in Florida – the primary enzootic vector to wild birds and the primary epidemic vector to humans of the Saint Louis encephalitis (SLE) virus. It has been experimentally demonstrated to be capable of transmitting West Nile virus (WNV). Its habit of feeding on both birds and humans gives it significant potential for transmission of zoonotic infections from birds to humans. It is also a vector of transmission of Eastern equine encephalitis (EEE), dog heartworm, and Avian malaria.