We have studied the response of the two closest relative strains M8 and M31 of Salinibacter ruber to environmental changes as the transition from exponential to stationary phase in a batch growth, and the submission to two different environmental stresses (dilution of the culture medium and temperature decrease). We monitored the changes in cultivability, ribosomal content by fluorescence in situ hybridization (FISH), and metabolic changes with high-field ion cyclotron Fourier transform mass spectrometry. In all cases, we could observe an important decrease in cultivability that was not accompanied by a decrease in FISH counts, pointing to a transition to viable but non-cultivable state rather than cell death. Furthermore, the metabolomic analyses indicated a common response of both strains to the different conditions assayed. Only a small portion of the detected masses could be annotated due to database constraints. Among them, the most remarkable changes could be attributed to modifications in the composition of the cell envelope, and especially in the cell membrane. We could track changes in the length or saturation of the fatty acids and in the composition of phospholipids involved in aminosugar, glycerolipid, and glycerophospholipid metabolic pathways.