The first preparatory drawings for this painting date from 1857 and were inspired by the artist's visit to the Roman Church of San Pietro in Vicoli, where a fresco from 1476 depicted a plague epidemic. At the time when Delaunay was painting his picture, the disease was no longer the scourge it had been for so long and he refers to it through a literary transposition: a passage from Jacobus de Voragine's Golden Legend telling the story of Saint Sebastian, which reads: "And then there appeared a good angel, who commanded a bad angel, armed with a pike, to strike the houses and each house had as many dead as the number of blows on the door".
Around a central void, closed in the background by a few houses, fugitives and the equestrian statue of Marcus Aurelius, the painter has arranged several plague victims, in the shadows lower left, counterbalanced by the two angels heralding terror, in full light, on the right. In the lower right-hand corner, two figures are huddled at the foot of the statue of its Aesculapius (the Roman god of medicine), partly visible in an alcove above them. In the upper left-hand corner, a procession of priests in white surplices is advancing behind a gilded processional cross.
Life and death, paganism and Christianity are therefore opposed in this painting which wavers between symbolism and fantasy and was one of the most acclaimed and commented works in the Salon in Paris in 1869.