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Chromohalobacter salexigens is a halophilic γ‐proteobacterium that responds to osmotic and heat stresses by accumulating ectoine and hydroxyectoine respectively. Evolution has optimized its metabolism to support high production of ectoines. We analysed the effect of an rpoS mutation in C. salexigens metabolism and ectoines synthesis. In long‐term adapted cells, the rpoS strain was osmosensitive but not thermosensitive and showed unaltered ectoines content, suggesting that RpoS regulates ectoine(s)‐independent osmoadaptive mechanisms. RpoS is involved in the regulation of C. salexigens metabolic adaptation to stress, as early steps of glucose oxidation through the Entner–Doudoroff pathway were deregulated in the rpoS mutant, leading to improved metabolic efficiency at low salinity. Moreover, a reduced pyruvate (but not acetate) overflow was displayed by the rpoS strain at low salt, probably …