Rescue charity ship Open Arms received the green light to set sail from the port of Barcelona on Wednesday but will not be allowed to return to the central Mediterranean to save migrants.
Spanish authorities in mid-January denied permission for the ship to leave Barcelona, arguing Spain has no maritime rescue jurisdiction off the Libyan coast where the Open Arms operated.
But Spanish migrant rescue charity Proactiva Open Arms which operates the ship said in a statement it had been authorised to head to the Greek islands of Lesbos and Samos to deliver "humanitarian material".
"After being blocked in the port for 100 days, it will set sail, but without authorisation to enter the SAR (search and rescue) zone of the central Mediterranean," it added.
Pope Francis criticised the Spanish government's decision to block the ship in Barcelona during an interview broadcast on March 31 on Spanish TV channel La Sexta, saying it was "a great injustice".
"Why is it done? So they drown?," he asked.
Proactiva Open Arms operates between Libya and southern Europe, coming to the aid of migrants who get into difficulties during the dangerous sea crossing from northern Africa. It says it has rescued nearly 60,000 lives since it was founded in 2015.
The decision to keep the Open Arms in Barcelona marked a change in policy for Prime Minister Pedro Sanchez's minority socialist government, which made international headlines shortly after it come to power in June by allowing another rescue boat, the Aquarius, to dock in Spain with more than 600 migrants on board after Italy and Malta refused them entry.