Saint Sebastian was a 3rd-century Roman officer who was condemned to be shot with arrows for his Christian beliefs. After healing from his wounds, he was eventually beaten to death, and his body was thrown into a sewer.

Simon Vouet does not depict the saint's martyrdom, but he alludes to it through the arrow that the figure holds. The French-born artist painted this work in Rome, where he lived from 1614 to 1627. Vouet was one of the most successful foreign painters in Italy, and he continued to enjoy a prestigious and influential career after his return to France. Vouet's Saint Sebastian shows the impact of the work of Italian painter Michelangelo Merisi da Caravaggio (known as Caravaggio), whose compositions often were limited to one figure or a few figures, shown in half length, set in obscure surroundings, and illuminated by a strong, raking light.