Epithermal mineralization was recently described in synrift volcanic rocks from the SE Afar Rift in Djibouti. To infer fluid sources in this system, coupled sulfur and strontium isotopic analyses were performed on mineralized samples from hydrothermal veins and stockwork zones. Mineralization includes gypsum and chalcedony, and/or quartz ± carbonate containing gold and sulfides. Sulfur isotopic compositions of sulfides and sulfates were determined using Multicollector-Inductively Coupled Plasma Mass Spectrometer (MC ICPMS); Laser Ablation MC ICPMS; and Continuous Flow Elemental Analyzer-Isotope Ratio Mass Spectrometry while strontium isotopes were determined by Thermal Ionisation Mass Spectrometry (TIMS) methods. Sulfur isotopic composition of sulfides (mainly pyrite) varies from − 9.2 to + 6.6‰. These values are classically reported for hydrothermal sulfides resulting from the mixing of variable S sources such as seawater sulfate and magmatic source. In addition, individual pyrite grains within the same sample show both positive and negative δ34S values suggesting multi-phase mineralization processes. Coupled sulfur and strontium isotopic compositions of seven sulfate samples hosted in (i) gypsum mound, (ii) evaporites, (iii) stockwork veins in sediments or in volcanic rocks were also investigated to characterize the sources of Sr and S. The δ34S values of the sulfate ranged from − 0.8 to + 14.3‰ while the 87Sr/86Sr ranged from 0.70389 to 0.70639 consistent with variable mixing ratios of Sr and S derived from volcanic sources and seawater-derived sulfate. This study shows that, although precious-metal deposition is related to low-sulfidation epithermal environment, both acidic fluid of magmatic and saline origins contributed to the hydrothermal system in the SE Afar Rift.