Background and Aim of the Work: Frailty is a state of reduced physiological reserve and is associated with increased susceptibility to disability. It is associated with a high morbidity and mortality. The aim of this work is to assess the association between the levels of homocystiene and C-reactive protein and frailty and to examine the ability of homocystiene as a new marker to detect frailty. Subjects and Methods: A total number of 104 elderly subjects (above 60 years old) were included in this study and they were subjected to history, examination, comprehensive geriatric assessment, and laboratory investigations including: C-reactive protein (CRP) and Homocystiene (Hcy). The patients were divided into frail and non-frail groups using Fried’s criteria as applied by Avila-Funes et al., 2008 and each group included 52 patients. Results: There was no significant difference between the two groups as regards age gender or smoking habits. But there were higher levels of CRP (>10 mg/dl) and homocystiene (>12 mmol/l) among frail cases and by comparing both homocystiene was more sensitive in detection of frailty. Conclusion: Frailty was associated with eleveted homocystiene and CRP and homocystiene is more specific than CRP in detection of frailty.