Love as a cause of deep human suffering is the most prevalent theme in the novel. No love exists without suffering in this novel; the two experiences intertwine. At the moment that a love affair begins, a death, a suicide, or an infidelity that breaks the heart of one or both lovers simultaneously takes place, signaling to the reader that love is a complex affair that rarely affects only the two individuals involved in the relationship at hand.

The novel is bookended by acts of suicide, and these deaths emphasize the ongoing theme of love as a cause of human suffering. First, at the start of the novel, Jeremiah de Saint-Amour dies by his own hand. Though his suicide is not specifically for love, but a choice Saint-Amour made motivated by his profound fear of old age; it is an act of self-love and self-protection.

Florentino Ariza suffers the most for love, and despite fifty years of disappointment and pain, he embraces his suffering as part of his fate. As he reflects on his reaction to the marriage of his love, Fermina Daza, to Urbino, he finds that his distress is pleasurable because the depth of his emotion enables him to maintain an emotional connection to Fermina: “That idea broke his heart, but he did nothing to suppress it; on the contrary, he took pleasure in his pain.