Four men and two women died in the inferno, which broke out in the early evening, Phnom Penh Municipal Police spokesman San Sok Seiha said, AFP reported.
It took a few hours for firefighters to extinguish the flames.
Authorities are investigating the cause of the blaze.
“We don’t know yet if there will be more victims,“ Sok Seiha said.
He said police were still waiting to enter the burnt-out club.
In December last year, a fire ripped through a casino on the Thai-Cambodian border, killing 26 people and forcing patrons to jump from ledges and windows to escape the flames.
Authorities said the Grand Diamond City hotel-casino fire in Poipet town was caused by an electrical fault.