Like other bacteria, Mycobacterium spp. have developed different strategies in response to environmental changes such as nutrient limitations and other different stress situations. We have identified candidate genes (rsb genes) from Mycobacterium marinum involved in the regulation of the activity of the alternative sigma factor, σF. This is a homolog of the master regulator of general stress response, σB, and the sporulation-specific sigma factor, σF, in Bacillus subtilis. The organization of these genes in M. marinum and B. subtilis is similar. Transcriptome and qRT-PCR data show that these genes are indeed expressed in M. marinum and that the levels of expression vary with growth phase and exposure to stress. In particular, cold stress caused a significant rise in the expression of all identified rsb and sigF genes. We discuss these data in relation to what is currently known for other Mycobacterium spp.