The mood of "The Birthmark" is initially foreboding as the reader learns of Aylmer's obsessive tendencies and disturbing dreams. Early in the story, Aylmer fixates so strongly on the birthmark that he cannot escape it whether he is asleep or awake. In the following passage, the narrator makes it clear that Aylmer's neurotic imagination turns the birthmark into a real-life problem:
In this manner, selecting it as the symbol of his wife’s liability to sin, sorrow, decay, and death, Aylmer’s sombre imagination was not long in rendering the birthmark a frightful object, causing him more trouble and horror than ever Georgiana’s beauty, whether of soul or sense, had given him delight.
In these first few pages, it becomes clear that the birthmark will be removed regardless of the consequences. As Aylmer performs optical illusions and tells Georgiana about his lofty goal, the mood lightens briefly before assuming an even darker aspect. In the final pages, the mood becomes bleak and hopeless. When Georgiana opens her eyes after drinking the elixir, Aylmer notices something very wrong:
A faint smile flitted over her lips when she recognized how barely perceptible was now that crimson hand which had once blazed forth with such disastrous brilliancy as to scare away all their happiness. But then her eyes sought Aylmer’s face with a trouble and anxiety that he could by no means account for.
Aylmer then learns that he has failed as a scientist; Georgiana is dying, their servant chuckles ominously at the scene, and the narrator takes over the storyline to warn the reader of the inevitable triumph of Nature over earthly attempts to achieve divinity. Words like "disastrous," "trouble," and "anxiety" clue the reader in about Georgiana's plight even before she explicitly says she is dying.