Sfax prosecutor spokesman Faouzi Masmoudi said the victim, aged in his early 40s, was fatally stabbed late Monday during a scuffle between local residents and migrants from sub-Saharan Africa.
Masmoudi said three suspects, from Cameroon according to initial information, had been arrested.
Locals in Sfax regularly protest the presence of the migrants and call for them to leave.
The tensions have led to deadly violence before. In late May police arrested three Tunisians on suspicion of stabbing to death a migrant from Benin.
Tunisia has seen a rise in racially motivated attacks on migrants and foreign students following President Kais Saied's comments in February accusing "hordes" of illegal migrants of bringing violence, crime and "unacceptable practices."
He also spoke of a "criminal plot" to change the country's demographic makeup.
With a population of 12 million, Tunisia hosts an estimated 21,000 migrants from other parts of Africa, representing 0.2 percent of the population.
While some migrants come to Tunisia to study, many use Sfax as a springboard for attempts to reach Europe by sea, usually to the Italian island of Lampedusa about 150km away.
Tunisians themselves have joined the exodus in a bid to flee the economic crisis in their country, which is highly indebted and in talks for a bailout loan from the International Monetary Fund.
Europe has offered funding to help assist Tunisia's efforts against illegal migration and boost the economy.
Saied has repeatedly rejected what he terms the "diktats" of the Washington-based IMF.
Tunisia Nabs Migrants After Stabbing Death
TUNIS — Three African migrants have been arrested as suspects in the stabbing death of a local man in Tunisia's coastal city of Sfax, a court spokesman said on Tuesday.
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