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The 1970s brought a new understanding of the biological and intellectual impact of environmental crises on human beings, and as efforts to prevent ecological and human degradation aligned, a new literature of sickness emerged. “Ecosickness fiction” imaginatively rethinks the link between ecological and bodily endangerment and uses affect and the sick body to bring readers to environmental consciousness. Tracing the development of ecosickness through a compelling archive of modern U.S. novels and memoirs, this study demonstrates the mode’s crucial role in shaping thematic content and formal and affective literary strategies. Examining works by David Foster Wallace, Richard Powers, Leslie Marmon Silko, Marge Piercy, Jan Zita Grover, and David Wojnarowicz, Heather Houser shows how these authors unite experiences of environmental and somatic damage through narrative affects that draw attention to ecological phenomena, organize perception, and convert knowledge into ethics. Traversing contemporary cultural studies, ecocriticism, affect studies, and literature and medicine, Houser juxtaposes ecosickness fiction against new forms of environmentalism and technoscientific innovations such as regenerative medicine and alternative ecosystems. Ecosickness in Contemporary U.S. Fiction recasts recent narrative as a laboratory in which affective and perceptual changes both support and challenge political projects.