This paper aims at investigating the ways in which Romantic poetry displays contemporary discourse about disease in the age of colonial expansion. Among various responses to infectious diseases, the two most prevalent views put emphases on the notions of “contamination” and “contagion” respectively. While some believed that most diseases could be prevented by the overall improvement of personal hygiene and living environments, others exposed deeper fear about the highly contagious aspect of infectious diseases encountered in the colonial areas. Percy Bysshe Shelley’s Queen Mab is a literary example that shows a strong belief in the possibility of healthy society in both physical and political terms. Shelley believes that, by extending Enlightenment ideas, the world can overcome the threats of diseases and recover a generally healthy state. Yet, Samuel Taylor Coleridge’s The Rime of the Ancient Mariner reveals deeper anxiety about the contagious power of infectious diseases. The collective death of the mariners can be due to a spread of a contagious disease such as the yellow fever. Despite the imperial discourse that highlighted the West’s contribution to the improvement of the entire world, infectious diseases nonetheless posed a profound threat to the colonial project.