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Cytochrome P450 monooxygenases (CYPs/P450s) are heme thiolate proteins present in species across the biological kingdoms. By virtue of their broad substrate promiscuity and regio- and stereo-selectivity, these enzymes enhance or attribute diversity to secondary metabolites. Actinomycetes species are well-known producers of secondary metabolites, especially <i>Salinispora</i> species. Despite the importance of P450s, a comprehensive comparative analysis of P450s and their role in secondary metabolism in <i>Salinispora</i> species is not reported. We therefore analyzed P450s in 126 strains from three different species <i>Salinispora arenicola</i>, <i>S. pacifica,</i> and <i>S. tropica</i>. The study revealed the presence of 2643 P450s that can be grouped into 45 families and 103 subfamilies. CYP107 and CYP125 families are conserved, and CYP105 and CYP107 families are bloomed (a P450 family with many members) across <i>Salinispora</i> species. Analysis of P450s that are part of secondary metabolite biosynthetic gene clusters (smBGCs) revealed <i>Salinispora</i> species have an unprecedented number of P450s (1236 P450s-47%) part of smBGCs compared to other bacterial species belonging to the genera <i>Streptomyces</i> (23%) and <i>Mycobacterium</i> (11%), phyla <i>Cyanobacteria</i> (8%) and <i>Firmicutes</i> (18%) and the classes <i>Alphaproteobacteria</i> (2%) and <i>Gammaproteobacteria</i> (18%). A peculiar characteristic of up to six P450s in smBGCs was observed in <i>Salinispora</i> species. Future characterization <i>Salinispora</i> species P450s and their smBGCs have the potential for discovering novel secondary metabolites.