Greece's coastguard said 59 migrants died early Wednesday after their boat capsized and sank off the Peloponnese, while around 100 others were rescued.
The accident occurred in international waters in the Ionian Sea and prompted an extensive rescue operation complicated by strong winds, the coastguard said earlier.
Along with navy vessels, the operation included an army plane and helicopter as well as six other boats that were in the area.
"Since very early Wednesday, an extensive rescue operation is underway off Pylos, after a fishing boat capsized with a large number of migrants onboard," the coastguard said.
Those rescued were being brought to Kalamata, though four in serious condition were transferred by helicopter to the port's hospital.
The coastguard said a surveillance plane with Europe's Frontex agency had spotted the boat Tuesday afternoon, but the passengers "refused any help".
It later said that none on board were wearing life jackets, and did not immediately disclose their nationalities.
Authorities said it appeared the migrants had departed from Libya and were heading for Italy.
Also Wednesday, Greece's port police said a sailboat in distress carrying about 80 migrants off Crete was rescued by a coastguard patrol and towed to port.
Greece along with Italy and Spain have long been the main landing points for the tens of thousands of people seeking to reach Europe from Africa and the Middle East.
Greece is also facing an increase of crossing attempts from Turkey on southern routes near the Cyclades islands and toward the Peloponnese peninsula, hoping to avoid patrols in the northern Aegean Sea.
Rescue operations are common, but last month the Greek government came under international pressure over video footage reportedly showing the forceful expulsion of migrants who were set adrift at sea.
Greece and other EU member states on the south and southeastern rim of the bloc say they are being unfairly tasked with managing arrivals of undocumented migrants.
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