"Those who pollute are not in the grace of God and can not take communion,'' Sepe told journalists.
His remarks came after cases of the local mafia burying cancer-inducing toxic waste around the city recently made headlines.
"We need to tell the truth to people about what happened. But we also need to stress the positive action that has already been taken. It's time for us all to work together and keep freeing our land of poisons," Sepe said.
He said he had ordered local priests, deacons and lay brothers to be aware of the Church's role in public ethics.
Sepe was speaking on the sidelines of Christian environmentalist group Greenaccord's annual meeting in Castel dell'Ovo, Naples.