An investigation into the cause of their deaths is ongoing, but a recent World Health Organization alert warns of a deadly influenza strain, including in Fiji where it is "particularly affecting young adults".
Michelle Paul, a 35-year-old mother-of-one from Fort Worth, Texas, died in a hospital on the island last week.
Family member Tracey Calanog told U.S. media outlet KVUE: "They knew something was going on with their body and were able to get to the hospital".
Their "amazing vacation", however, turned into a nightmare when the parents of two - David and Michelle share a 2-year-old son and also raise David's daughter from a past relationship - came down with an unknown illness, sending them both to the hospital.
"CDC has received a request for assistance from the Ministry of Health in Fiji regarding the death of an American couple in Fiji of an unidentified illness", the CDC said in a statement.
Michelle was the first to die.
However, despite the best efforts of health professionals, Michelle died and David followed shortly after during the Memorial Day weekend, before he could be airlifted to Australia for treatment, possibly from pneumonia.
Texas residents David and Michelle Paul arrived in Fiji on May 22, Fiji's Ministry of Health and Medical Services said in a statement. "At this point, we are not aware of any specific public-health threat to the community".
The U.S. Embassy in Fiji would not comment on the deaths but confirmed the Fijian government had issued a warning about a risky flu season that was affecting the region.
Calanog said the couple - a former Air Force veteran and former student athlete - were "very physically fit".
The department is keeping an eye on the investigation by local authorities.
"They were planning an awesome vacation", Calanog said.
"We know that Michelle and David are with us in Zooey", Calanog said, reported ABC 7.
Calanog said the cause of death must be determined before the bodies are returned to the United States, and if an infectious illness is found to be the cause, their bodies will have to be cremated. "We know Michelle and David are with us in Zooey".