Though cosmicism appears deeply pessimistic, H.P. Lovecraft thought of himself as neither a pessimist nor an optimist but rather a "scientific" or "cosmic" indifferentist, a theme expressed in his fiction. In Lovecraft's work, human beings are often subject to powerful beings and other cosmic forces, but these forces are not so much malevolent as they are indifferent toward humanity.

Often in Lovecraft's works the protagonist is not in control of his own actions, or finds it impossible to change course. Many of his characters would be free from danger if they simply managed to run away; however, this possibility either never arises or is somehow curtailed by some outside force, such as in "The Colour Out of Space" and "The Dreams in the Witch House"

Lovecraft made frequent reference to the "Great Old Ones": a loose pantheon of ancient, powerful deities from space who once ruled the Earth and who have since fallen into a deathlike sleep. This was first established in "The Call of Cthulhu", in which the minds of the human characters deteriorated when afforded a glimpse of what exists outside their perceived reality. Lovecraft emphasized the point by stating in the opening sentence of the story that "The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents."

Many of his characters are driven by curiosity or scientific endeavor, and in many of his stories the knowledge they uncover proves Promethean in nature, either filling the seeker with regret for what they have learned, destroying them psychically, or completely destroying the person who holds the knowledge.