What influence did climate have on disease in Late Antiquity? Natural archives of pre-instrumental temperature indicate significant summer cooling throughout the period. The coolest stretch spanned the 6th and 7th c., and corresponds startlingly to the appearance of the Justinianic Plague in the Mediterranean region. Drawing on principles from landscape epidemiology, this paper marries textual evidence for disease with palaeoclimatic data, in order to understand how gradual and dramatic climatic change, the 535–50 downturn especially, may have altered the pathogenic burden carried in Late Antiquity. Particular attention is paid to the Justinianic Plague, but the potential impacts of a changing climate on malaria and non-yersinial, non-plague, epidemics are not overlooked.