There is a general agreement that fault-fracture meshes exert a primary control on fluid flow in both volcanic/magmatic and geothermal/hydrothermal systems. For example, in geothermal systems and epithermal gold deposits, optimally oriented faults and fractures play a key role in promoting fluid flow through high vertical permeability pathways. In the Southern Volcanic Zone (SVZ) of the Chilean Andes, both volcanism and hydrothermal activity are strongly controlled by the Liquine-Ofqui Fault System (LOFS), an intra-arc, strike-slip fault, and by the Arc-oblique Long-lived Basement Fault System (ALFS), a set of transpressive NW-striking faults. However, the role that principal and subsidiary fault systems exert on magma degassing, hydrothermal fluid flow and fluid compositions remains poorly constrained. In this study we report new helium, carbon and nitrogen isotope data (He-3/He-4, delta C-13-CO2 and delta(15) N) of a suite of fumarole and hot spring gas samples from 23 volcanic/geothermal localities that are spatially associated with either the LOFS or the ALFS in the central part of the SVZ. The dataset is characterized by a wide range of He-3/He-4 ratios (3.39 Ra to 7.53 Ra, where Ra = (He-3/He-4)(air)), delta C-13-CO2 values (-7.44% to -49.41%) and delta(15) N values (0.02 parts per thousand to 4.93 parts per thousand). The regional variations in He-3/He-4, delta C-13-CO2 and delta(15) N values are remarkably consistent with those reported for Sr-87/Sr-86 in lavas along the studied segment, which are strongly controlled by the regional spatial distribution of faults. Two fumaroles gas samples associated with the northern "horsetail" transtensional termination of the LOFS are the only datapoints showing uncontaminated MORB-like He-3/He-4 signatures. In contrast, the dominant mechanism controlling helium isotope ratios of hydrothermal systems towards the south appears to be the mixing between mantle-derived helium and a radiogenic component derived from, e.g., magmatic assimilation of He-4-rich country rocks or contamination during the passage of the fluids through the upper crust. The degree of He-4 contamination is strictly related with the faults controlling the occurrence of volcanic and geothermal systems, with the most contaminated values associated with NW-striking structures. This is confirmed by delta(15) N values that show increased mixing with crustal sediments and meteoric waters along NW faults (AFLS), while delta C-13-CO2 data are indicative of cooling and mixing driving calcite precipitation due to increased residence times along such structures. Our results show that the structural setting of the region exerts a fist-order control on hydrothermal fluid composition by conditioning residence times of magmas and thus promoting cooling/mixing of magmatic vapor, and therefore, must be taken into consideration for further geochemical interpretations. ; FONDECYT grant 1130030 FONDAP project "Centro de Excelencia en Geotermia de los Andes, CEGA" 15090013 MSI "Millennium Nucleus for Metal Tracing Along Subduction" NC130065 MEXT, Japan 15H05830 FONDECYT Iniciacion grant 11130351 MECESUP program