We examined whether a systemic marker of oxidative stress, F 2-isoprostanes (F 2-IPs), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition (Health ABC) study, F 2-IPs and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole-body dual-energy X-ray absorptiometry and regional adiposity by abdominal and thigh computed tomography scans at baseline and 5-year follow-up. ANOVA models were estimated to examine associations between F 2-IP tertiles and baseline adiposity and changes in body composition. Median F 2-IPs was 54.3pg/ml; women had significantly higher levels than men (61.5vs. 48.9pg/ml, P 0.001). F 2-IPs were associated with higher levels of adiponectin, leptin, and tumor necrosis factor-α (TNF-α). Positive associations were found between F 2-IPs and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow-up, women in the highest vs. lowest F 2-IP tertile exhibited significant loss of weight (lowest tertile: 1.1kg, highest tertile: 2.7kg, P 0.05). In conclusion, F 2-IPs were associated with measures of total and regional adiposity in women alone and these associations were partially explained by adipocytokines. F 2-IPs predicted loss of total adiposity over time among women.