Abstract There is growing evidence that positive affect may influence health and immune function, although few studies have examined links between positive affect and immune processes in clinical populations. The purpose of this study was to examine whether positive affect is associated with changes in proinflammatory cytokines in cancer patients undergoing radiation treatment. Subjects were 50 individuals with early-stage breast and prostate cancer who completed psychosocial questionnaires and provided blood samples at seven time points before, during, and after radiation treatment. Positive affect was assessed before treatment onset using the CES-D (Center for Epidemiological Studies Depression Scale). Blood samples were assayed for serum levels of proinflammatory cytokines IL-1β and IL-6. Patients with higher levels of positive affect before treatment exhibited higher mean levels of IL-1β and IL-6 during radiation treatment (all ps < .05). Results suggest that positive affect enhances the acute inflammatory response to radiation treatment, perhaps facilitating tissue repair processes.