The UN's refugee agency said 16 bodies, including two babies, had been found.
The UNHCR has said all ships using the Mediterranean should be ready to assist such vessels, as thousands continue to flee North Africa in inadequate boats.
Nato has denied claims that its naval units left dozens of migrants to die aboard another boat in distress.
It said it was unaware of the plight of the boat, which reportedly was adrift for more than two weeks.
The Guardian newspaper said 61 of the 72 people on board the boat died of hunger or thirst, despite being spotted by a military helicopter and Nato ship.
'Extra vigilant' journey
The UNHCR said migrants arriving on the Italian island of Lampedusa had reported seeing the boat carrying some 600 people foundering shortly after leaving the port at Tripoli on Friday.
Ms Wilkes said it appeared that hundreds of people were missing - bodies were seen floating in the sea and those of 16 people, including two babies, have been washed ashore.
She said it was unclear whether anyone was looking for the missing people, but that Nato was not involved in the operation.
The nationalities of the passengers was also not known, but many of those waiting in Lampedusa were Somali, she said.
The International Organisation for Migration (IOM) said it had spoken to one Somali woman who had been on board the ship with her four-month-old baby. The baby died and the mother swam to shore, where she boarded another boat heading to Europe.
Ms Wilkes said "hundreds if not more than a thousand people" have died making the "treacherous journey" in the past few months.
The agency has said all ships should be prepared to offer immediate help to any boat carrying migrants.
"We are calling on all ships in the Mediterranean - whether commercial, military or otherwise - to be extra vigilant and consider on sight that these boats are in distress and needing rescue," said the spokeswoman.
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