Background: Few studies have examined whether community factors mediate the relationship between patients surviving cancer and future development of sepsis. We determined the influence of community characteristics upon risk of sepsis after cancer, and whether there are differences by race. Methods: We performed a prospective analysis using data from the REasons for Geographic and Racial Differences in Stroke cohort years 2003 to 2012 complemented with county-level community characteristics from the American Community Survey and County Health Rankings. We categorized those with a self-reported prior cancer diagnosis as “cancer survivors” and those without a history of cancer as “no cancer history.” We defined sepsis as hospitalization for a serious infection with ≥2 systemic inflammatory response syndrome criteria. We examined the mediation effect of community characteristics on the association between cancer survivorship and sepsis incidence using Cox proportional hazards models adjusted for age, sex, race, and total number of comorbidities. We repeated analysis stratified by race. Results: There were 28 840 eligible participants, of which 2860 (9.92%) were cancer survivors, and 25 289 (90.08%) were no cancer history participants. The only observed community-level mediation effects were from income (% mediated 0.07%; natural indirect effect [NIE] on hazard scale] = 1.001, 95% confidence interval [95% CI]: 1.000-1.005) and prevalence of adult smoking (% mediated = 0.21%; NIE = 1.002, 95% CI: 1.000-1.004). We observed similar effects when stratified by race. Conclusion: Cancer survivors are at increased risk of sepsis; however, this association is weakly mediated by community poverty and smoking prevalence.