In a visit stripped of the usual pomp of papal travel, Francis will cast a wreath into the sea and hold a mass of mourning with a simple cross made from the wood of rickety fishing boats that migrants arrive on.
The pope will visit the same pier where migrants first set foot on dry land after landing from Libya or Tunisia in journeys that often begin in impoverished and war-torn parts of Africa and the Middle East.
The pope is expected to fly into Lampedusa, which is closer to North Africa than to the Italian mainland, at around 0715 GMT and leave at 1045 GMT.
Around 50 migrants -- some of them Muslim -- will meet with the leader of the world's 1.2 billion Catholics, out of more than 100 currently on the island.
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Cardinal Antonio Maria Veglio, head of the Vatican's migrant department, said he hoped the visit would prompt "concrete concern and solidarity to improve situations that have become inhuman and unacceptable".
Local mayor Giusi Nicolini said she wanted more help in dealing with migrant arrivals from "the rest of the country and Europe", denouncing the deaths at sea as "a great injustice in the Mediterranean".
One inhabitant has offered his converted Fiat car to be used as a "popemobile" during a trip in which the Vatican has insisted that no politicians should accompany the pope in a break with usual protocol.
There has been an increase in arrivals on Lampedusa in recent weeks because of improved weather conditions, with around 4,000 arriving so far this year -- three times more than during the same period in 2012.
Since 1999, more than 200,000 people have arrived on Lampedusa -- making it along with the Greece-Turkey border one of biggest gateways for undocumented migrants and refugees into the European Union.
The visit has been praised by many including Andrea Riccardi, founder of the Catholic charity Sant'Egidio, who wrote in the Corriere della Sera daily that it meant "the Church of the poor is looking South".
The United Nations High Commissioner for Refugees estimates 40 people have died so far in 2013 -- most by drowning -- trying to cross from North Africa, while around 500 were reported dead or missing in 2012.