Investigations of the biological effects of climate change in past societies can increase our understanding of diverse human adaptations to environmental instability. Individuals from ecologically marginal regions are particularly susceptible to climate-induced resource stress. In this study, we create and test an integrated paleoenvironmental and bioarchaeological model of the biosocial effects of environmental change on nutritionally based health outcomes. We present new evidence for scurvy (severe vitamin C deficiency) in ancient human remains (N = 187) from the hyper-arid northern Atacama Desert, South America, which we interpret as indicating episodes of low dietary diversity. Skeletal evidence for scurvy was found to increase significantly across the Archaic-Formative transition (c. 3500–1500 BP). Previous paleoenvironmental and isotopic research indicates that this transition is also marked by increased frequency of ENSO events, and a dietary shift to horticulturalism rather than marine-focused hunting and gathering. Here we build on this modeled environmental and subsistence change, and propose that increased ENSO events may have contributed to social adaptations to resource insufficiency, cyclicity of marine resource use, and ultimately an environment favorable to periodic micronutrient famines and the osteological manifestations of scurvy.