Police said 17 relatives were in the house when the shootings were reported around 10 p.m. Thursday in Jupiter, a small, well-off beach town about 90 miles north of Miami that is best known as a home to celebrities including Michael Jordan and Burt Reynolds.
Jupiter Police Sgt. Scott Pascarella said officers were looking for Paul Michael Merhige, 35, of Miami. Merhige is a cousin of the 6-year-old victim, Makayla Sitton, and has no criminal record, police said.
The others killed were Merhige's twin sisters, Carla Merhige and Lisa Knight, 33, and an aunt, Raymonde Joseph, 76, according to police.
Authorities said a fifth victim, Merhige's brother-in-law Patrick Knight, was being treated at a hospital. His condition was not available. Another man, Clifford Gebara, 52, was grazed by a bullet and was treated by paramedics on the scene and released.
Police across South Florida and the U.S. Marshals Service were searching for Merhige. Pascarella said Merhige is believed to be driving a blue 2007 4-door Toyota Camry with Florida license plate W42 7JT.
Pascarella said police received a 911 call from a neighbor shortly after 10 p.m. Police then received a second 911 call from someone within the home.
Pascarella said the shootings took place inside the house. He said that sometime after Thanksgiving dinner, Merhige left the residence and returned shortly afterward with a handgun.
"What led to this incident, we're not quite sure," said Pascarella. "It did not appear there was any altercation prior to this shooting."
Pascarella said there was an "ongoing resentment" in the family, but didn't know the nature of the problem or whether the victims were specifically targeted.
Police said the home was owned by Jim Sitton, a photojournalist for WPTV-TV and father of the little girl killed. Sitton told WPTV his daughter was in bed when she was shot. He was at the party at the time of the shooting but was not wounded.
Yellow crime scene tape was stretched around Sitton's salmon-colored house, located in a well-kept subdivision of stucco homes. Several cars were parked in the driveway, and a crime scene van sat in front.
Sitton told local media that his daughter was supposed to perform Friday in a holiday production of "The Nutcracker."
"God packed a lot of sweetness into that little body," Sitton said. "She's just our life. I don't know how we are ever going to recover."
The relationship between Sitton and Paul Merhige was unclear, police said.
Phone calls to a number listed for Paul Merhige were not answered. A phone call to Sitton was also not returned.
Neighbors in the Palm Beach County community were shocked.
"Our kids walk the streets by themselves," said 67-year-old Nicole Kemp, who did not know any of the victims. "I thought it was the safest place to live. I guess it doesn't matter, if there's a maniac here."
It's unclear where the adult victims lived. Carla Merhige was a real estate agent in Miami, said a co-worker.
"She was a wonderful agent," said Joanna Sherman, a manager at Coldwell Banker Residential real estate. "She was very active in the community and in charities. She was just a genuine, beautiful individual. She always had a smile for everybody."
Associated Press writers Suzette Laboy and Tamara Lush contributed to this report.