"We suppose" that they drowned, a spokeswoman for the coastguards told AFP, adding however that rescue forces were still surveying the seas near Spain's Alboran Island where the boat was found drifting, to try and find any survivors.
If the missing are confirmed dead, this will be the deadliest sea crossing in this part of the Mediterranean since the start of the year.
So far, 60 migrants have died trying to cross the waters to Spain from north Africa since January, according to the International Organization for Migration (IOM).
The survivors, three men aged 17 to 25 from sub-Saharan Africa, "explained that more than 50 people were on board the rubber boat which had been drifting for several days after leaving the northern coast of Morocco," the coastguards said in a statement.
They were taken to hospital in Almeria in southern Spain, and are still too weak to tell a detailed story of what happened, the spokeswoman said.
According to the IOM, 6,464 people reached Spain after crossing the Mediterranean between January 1 and June 25.
Altogether, at least 2,247 people have died or are missing after trying to cross the sea into Europe via Spain, Italy or Greece this year, the IOM says.
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