Frailty is a complex clinical state in elderly population and is associated with adverse health outcomes. No diagnostic biomarker has been identified for frailty so far. In our previous study we had shown that SIRT1 and SIRT3 are associated with low circulating levels in case of frail, even after adjusting various confounders. As sirtuin (SIRT) proteins are the family of seven isoforms, so quantifying the levels of SIRT4-7 would further expand our knowledge regarding the role of sirtuins in frailty. The aim of this study was to estimate the level of other sirtuins (SIRT4-7) in frail and assess their potential utilization as protein marker to detect frailty in early stage. Level of SIRT4-7 in serum of 166 frail and non-frail subjects were determined using surface plasmon resonance technology and western blot experiments. In the cross sectional study, it was observed that the levels of SIRT5, SIRT6 and SIRT7 were significantly lower in case of frail as compared to non-frail individuals. After multivariable regression analysis only SIRT7 level was found to be significantly lower in case of frail. Receiver operating characteristic (ROC) analysis revealed that SIRT5 and SIRT6 were able to detect in the frail individuals with moderate accuracy. It can be summarized that after analysis of seven isoforms of sirtuin in serum with frailty, SIRT1 and 3 can be used as a potential protein marker for frailty and other SIRTs 2,4,5,6,7 are not strongly associated with frailty.