Several two-component systems of Streptomyces coelicolor, a model organism to study antibiotic production in Streptomyces, affects the expression of the bfr (SCO2113) gene, which codifies for a bacterioferritin, a protein involved in iron storage. The ∆bfr mutant has a delay in morphological differentiation and pigmented antibiotic production (actinorhodin and undecylprodigiosin) on complex media. The effect of iron in minimal medium was also tested in the wild type and the ∆bfr mutant, and we observed different production of the two pigmented antibiotics in minimal medium, with differences between strains depending on iron concentration and the medium (solid or liquid). Contrary to expected, no intracellular iron differences were detected between the two strains, but there is a higher level of reactive oxygen species in the ∆bfr mutant and a higher tolerance to oxidative stress. Proteomics analysis showed no variation in iron response proteins and a lower abundance of proteins related to actinorhodin, ribosomal proteins and others related to secondary metabolism production and differentiation. On the contrary, it revealed a higher abundance of proteins related to different kind of stresses such as respiration and hypoxia, among others. The bacterioferritin of S. coelicolor is a new element in the complex regulation of the secondary metabolism in S. coelicolor and iron acts as a signal to modulate the biosynthesis of active molecules.