This chapter examines space and time in the writings of Edgar Allan Poe that deal with pandemic disease. Recent studies of Poe in relation to place (e.g., Philip Edward Phillips and J. Gerald Kennedy and Jerome McGann) concentrated on contextualizing Poe’s oeuvre in terms of its human geographies, how places and spaces are manifested in his works, and how those works can, in turn, be mapped and remapped on to fictive, historical, actual, and imaginative locations. The recent pandemic has sensitized us anew to the ways in which Poe used cultural geography under the spatiotemporal pressures of epidemic disease. This chapter interprets Poe’s four tales that were explicitly set during pandemics in light of the recent pandemic and demonstrates how they reveal the social, political, and perceptual pressures of epidemic disease. Through this analysis, the essay demonstrates that Poe figured these periods of pandemic as pathoregimes, a term that I have coined to denote a period in which a disease seems to “rule” for a period over a population. The essay concludes with an examination of what Poe’s pestilential spatial logic has to teach us about modern pandemics and the meanings that pandemics produce.