This study comprehensively investigates H2 loss resulting from injecting two gas mixtures: I (60% H2 + 30% CH4 + 5% N2 + 5% CO2) and II (60% H2 + 30% N2 + 5% CH4 + 5% CO2) into an aqueous solution containing 20,000 ppm sodium chloride and 100 ppm acetic acid (a microbial by-product of acetogenesis) within Bandera clay-rich sandstone reservoirs. Conducted at 42 °C and 1350 psi, various analytical techniques, including X-ray diffraction (XRD), Scanning Electron Microscopy with Energy Dispersive X-ray (SEM-EDX) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, porosity and permeability assessments, pH and ion analysis, and gas chromatography, were utilized to assess the relevant properties of rocks, formation water, and gas content before and after 50 days treatment. The results indicate minimal sample reactivity, with dissolution primarily affecting dolomite and albite minerals. On average, porosity increased by 19% in formulation I and 15% in formulation II, while permeability decreased by 4.7% in formulation I and 5.3% in formulation II. In formulation I, H2 fraction decreased by 2.79%, CH4 increased by 7.15%, and CO2 decreased by 9.36%, with N2 remaining constant, whereas in formulation II, H2 only decreased by 1.3%, CH4 increased by 19.22%, and CO2 decreased by 3.58%, with N2 remaining consistent. Overall, the N2 cushion gas condition (i.e., formulation II) slightly outperformed CH4 in minimizing H2 losses. This study thus provides significant insights into potential H2 loss within a microbial-by-product-rich environment for underground hydrogen storage.