Objectives: Frailty status is associated with altered glucose-insulin dynamics. Here, we sought to investigate whether alteration in the dynamics of other circulating energy metabolism hormones after oral glucose is associated with frailty status. Design: Substudy of older women in a prospective cohort. Setting: Baltimore, Maryland. Participants: Seventy-three community-dwelling women aged 84-95 years without a diagnosis of diabetes who were enrolled in the Women's Health and Aging Study II. Measurements: We examined stimulus-response dynamics of free fatty acids (FFA), gut- (ghrelin,GLP-1) and adipocyte-derived hormones (leptin, adiponectin, resistin), growth hormone (GH), insulin-like growth factor 1 (IGF-1), and interleukin-6 (IL-6) at 0, 30, 60, 120, and 180-minutes after a 75-g glucose challenge according to frailty status (non-frail, pre-frail, or frail). Results: On average, frail women had higher fasting levels of glucose-raising hormones (FFA, resistin, GH, and IL-6) and lower fasting levels of glucose-lowering hormones (ghrelin, adiponectin, GLP-1 and IGF-1) versus non-frail women but these results were not statistically significant. Frail women also had higher fasting levels of leptin with relative adiposity compared to their counterparts, suggestive of leptin-resistance. Integrated area under the curve (AUC) values for each hormone followed similar trends by frailty status. After age and BMI adjustment, frail versus non-frail women were more likely to be in the lowest tertile of fasting ghrelin levels and 120-min ghrelin levels (both p<0.05) in logistic regression analyses. No large differences were found for other hormones in adjusted models. Conclusions: Our findings suggest dysregulation of the orexigenic hormone ghrelin in the frailty syndrome. Further studies are needed to explore the role of ghrelin dysregulation in the clinical manifestation of frailty.