Iconographic images and worship of the martyr Saint Sebastian - reputedly killed during the anti-Christian purges of the Roman emperor Diocletian but brought back to life by Saint Irene - were common during the fifteenth century. However, Mantegna diverged from traditional representations of the saint through numerous references to antique landscapes and architecture (again, an ironic homage given the identity of Sebastian's killers). He further references the ancient heritage of Renaissance painting and sculpture with his use of the classical contrapposto pose, and idealized musculature and physique, to represent Saint Sebastian's body, alike that of Greek statuary. The scene of a saint pierced with arrows also became a metaphor for the Black Death during the medieval era, for which reason Saint Sebastian became a patron saint of plague victims. The image of a ravaged body resonated with the Italian citizens of the fourteenth century, when the Black Death peaked in Europe, and Saint Sebastian remained an icon for centuries to come.
Martyr Sebastian is tied to the ruins of a Corinthian column, pierced with numerous arrows. Behind him are a profusion of Roman ruins, while to the bottom right two grim assassins stand with a quiver of arrows (interestingly, the man holding the arrows is rumored to represent Mantegna himself, a curious sort of self-homage). The color scheme of the painting primarily consists of light browns and skin tones, with a light blue background.