Pathogenic bacteria such as Acinetobacter baumannii encounter multiple environments over its lifetime and, like all bacteria, is forced to cope with harsh environmental stresses. These stress responses are coordinated by alternative sigma factors (s) of RNA polymerase, which direct RNA polymerase to specific promoters, thereby transcribing specific sets of genes. A. baumannii is a critically important pathogen that highly resistant to external stressors, yet it lacks a well-known sigma factor involved in general stress response, sS (RpoS). In this study, we demonstrate that an extracytoplasmic function s factor (sX) belonging to the ECF037 class, is necessary not only for coping with frequently encountered stressors such as desiccation, cold, heavy metals, starvation, oxidative stress but also for antibiotic tolerance and successful virulence. Transcriptomic and promotor sequence analysis revealed that sX regulon more closely resembles thesS regulon than sE of Escherichia coli as indicated by down regulation of several well-known sS-dependent genes such as otsA, katE. In contrast, inactivation of sX resulted in up to a 500-fold increase in expression of genes involved in DNA repair, such as alkB and ada. Mutagenesis analysis showed that cells lacking sx showed a ~10-fold decreased mutation rate in A. baumannii compared to wild-type. Our results provide evidence for novel functions of sX and that it acts a gate keeper for balancing increased general stress protection and decreased side effects of abundant DNA repair proteins.