The complex debates on the relationship between science and literature in the 19th century are marked by numerous misprisions on the part of scholars and authors alike. The study shows how Auguste Comte, Hippolyte Taine, and Ernest Renan attempted to compensate for scientific deficits by literary means. Vice versa, Honoré de Balzac, the brothers Goncourt, and Emile Zola attempted in their theoretical writings to use reconceptualizations and innovative presentation methods to confer specifically scientific qualities on the way their novels could be read and experienced. Paradoxically, at the end of the discussion aesthetic autonomy and artistic subjectivity stand affirmed.