In Bread and Wine, Catholicism is largely transplanted onto socialism, and socialism is raised to the form of a religion. Pietro Spina, who takes on the guise of being priest Don Paolo Spada, is a devoted socialist. Returning to Italy in the early 1930s, as fascism is on the rise, he must pretend to be a priest to travel incognito. Silone endows Spada with the qualities of a holy figure. For example, in his role as a priest, he saves Bianchina from death as she is suffering from the aftermath of an abortion. Pointedly, he absolves the woman of guilt for an act that would have been condemned by a Catholic priest. In so doing, he practices a kind of religion that is far different from the Catholic doctrine.

The true Christ-like figure in the novel is Luigi Murica, a socialist who dies for the cause. Toward the end of the book, Luigi and Don Paolo sit down to a meal of bread and wine together, and Don Paolo reveals his true identity to Luigi. After the meal, Luigi says that he has "confessed" (238). The religious symbolism of this meal, which resembles the Last Supper, is unmistakable. Luigi, who sacrifices himself for socialism and for the betterment of his people, has become a sacrificial, Christ-like figure who has been blessed by Don Paolo. The author suggests that the socialist martyr is the true hero.

A related theme is the way in which any form of religion or morality is only valid if it serves to help humanity. Don Paolo writes to Cristina at the end of the book, "Our love, our disposition for sacrifice and self-abnegation are fruitful only if they are carried into relations with our fellows" (257). In other words, religion and creeds such as socialism are only productive if they help humanity. In this book, the author criticizes both organized religion and dogmatic creeds such as communism and fascism, as they don't really aim to help others. Instead, the author asserts that any valid form of creed or religion must help people. The heroes of the book are those, such as Luigi, whose beliefs allow them to truly serve others.