The Organisation for Security and Cooperation in Europe said on Tuesday it had lost contact with a four-member team in the restive Ukrainian city of Donetsk.
Their disappearance comes more than a month after another OSCE team of military observers was captured by pro-Moscow rebels in eastern Ukraine and held in the flashpoint city of Slavyansk for over a week.
"The team was on a routine patrol east of Donetsk when contact was lost (on Monday evening)," the Vienna-based OSCE said in a statement about the latest incident.
"We have been unable to re-establish communication until now."
It said the four were international members of its Special Monitoring Mission but did not disclose their nationalities.
Fierce fighting erupted in Donetsk on Monday when Ukrainian government forces launched air strikes against pro-Russian separatist gunmen who seized the airport in the eastern industrial city.
The local mayor said 40 people had been killed, including two civilians and the rest combatants.
Over 1,000 observers from the OSCE and other international bodies had been in Ukraine to monitor Sunday's presidential election, which was won by billionaire tycoon Petro Poroshenko.
The Special Monitoring Mission currently has 210 unarmed civilian members, whose job is to meet with local and national authorities as well as ethnic and religious groups and non-governmental organisations.
It was approved by all states including Russia in March.
Its headquarters are in Kiev, with monitors deployed in teams of 10 across the country including flashpoint areas in the east and south with large ethnic Russian populations.
Eight members of the OSCE's military verification mission -- staffed by experts from member states -- were kidnapped in Slavyansk on April 25. One was released two days later and the others on May 3.
The OSCE, which began life in the 1970s as a forum for East-West dialogue during the Cold War, has emerged as a key player in the crisis in Ukraine.
It has sponsored a peace roadmap calling for national dialogue but the Kiev government has refused to involve the armed rebels and so far no progress has been made in three rounds of talks.
In all, the OSCE has nine different fields of activity including the election observation mission and a human rights assessment mission.