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Cotton production is negatively affected by both biotic (diseases and insects) and abiotic (high temperature, salinity, water deficit, and extreme pH) factors. Soil-borne diseases, especially wilts and rots, significantly reduce cotton yield. Thus, we aimed to isolate and identify multi-stress tolerant bacterial antagonistic agents (AGAs) against two major soil-borne pathogens, Macrophomina phaseolina and Fusarium oxysporum. A total of 132 isolates with distinct morphologies were recovered from 25 different rhizospheric soil samples of cotton. A dual culture plate and broth assay confirmed the antagonistic activity of the isolates against these phytopathogens. Four selected AGAs thrived in salt stress induced by different NaCl concentrations, up to 1.71 M, except for isolate 62, which survived up to 0.85 M. Under osmotic stress, all the AGAs were tolerant of up to −1.03 MPa. Similarly, all the AGAs were able to survive over …