The delegation was in the western city of Zintan to work on a case against Saif Al-Islam Gadhafi, the captive son of the deposed and late leader Moammar Gadhafi.
ICC President Sang-Hyun Song issued a statement saying he was "very concerned" about the missing staff as there had been no contact with them since Thursday.
"These four international civil servants have immunity when on an official ICC mission," Song wrote. "I call on the Libyan authorities to immediately take all necessary measures to ensure their safety and security and to liberate them."
The younger Gadhafi was named in an ICC warrant on charges of overseeing the killing of anti-government protesters that led to his father's ouster and he was captured in November.
Libyan officials are challenging the international court's jurisdiction, saying Gadhafi should be tried in a Libyan court.