Frailty is a progressive physiologic decline in multiple body systems, characterized by loss of function, loss of physiologic reserve, and increased vulnerability to disease and death. This condition is induced by a complex and multifactorial interaction between genetic, biological, physical, psychological and environmental factors. To understand the interplay between the age-related decline of the immune response, and the upregulation of the inflammatory response, the so called inflammaging, we investigated the role of different inflammatory mediators on frailty status in the elderly. The study was performed in a population of 180 older adults (≥65years), who were classified according to Fried's frailty phenotype. Plasma concentrations of neopterin, tryptophan, kynurenine, phenylalanine, tyrosine as well as kynurenine/tryptophan (Kyn/Trp) and phenylalanine/tyrosine (Phe/Tyr) ratios were analyzed as immune stimulation biomarkers. In addition, nitrite and C-reactive protein levels were measured as indicators of nitric oxide production and acute inflammation, respectively. Significant increases in neopterin, C-reactive protein and Kyn/Trp ratio, and decreases in tryptophan and nitrite concentrations in frail individuals compared with non-frail group were found. Both Kyn/Trp and Phe/Tyr ratios were significantly and positively correlated with neopterin. A positive correlation between kynurenine and tryptophan was also observed. Four parameters, i.e., neopterin, tryptophan, nitrite and C-reactive protein, were found to be strongly related to frailty status, although only nitrite confirmed its role of predictor after multiple regression analysis, supporting its use as a potential biomarker of frailty. Further investigation is required to strengthen the consistence and reproducibility of these findings, and to establish this parameter as a clinical biomarker of frailty.