This study analyzes how Doomsday Book (1992), by Connie Willis, constructs a symbolic grammar of compassion in contexts of collapse through the juxtaposition of two pandemics: the Black Death of the fourteenth century and a future epidemic in twenty-first-century Oxford. Through an interdisciplinary methodology that integrates history, medicine, anthropology, literature, and theology, the study approaches the semantic complexity of this speculative fiction from a transversal perspective which, far from reducing the work to a single analytical category, allows an exploration of the enduring human constants in the face of catastrophe. The article offers an original reading of the novel’s diptych structure as a form of mediation between possible worlds rather than a mere temporal parallelism. Among its main findings, it highlights that compassion—embodied in characters facing extreme situations—functions as a universal language and as an ethical principle of resistance to suffering. Thus, Doomsday Book transcends the boundaries of science fiction to present an ethical, aesthetic, and communicative reflection on meaning, care, and hope in times of crisis.