The antimicrobial activity of phycocyanin extracted from Anabaena oryzae SOS13 was assayed against 4 pathogenic bacteria using agar well-diffusion assay and using benzyl Penicillin, Clindamycin, Ofloxacin and Doxycycline as positive controls. The concentration inhibiting 50% bacterial growth and the minimum inhibition concentration (MIC). The mode of action of phycocyanin on bacteria was explored using electron microscopy (SEM & TEM). Phycocyanin from Anabaena oryzae SOS13 has α and β subunit corresponding to 14 and 24 kDa, with an isoelectric point near pH 6. Agar well diffusion assay revealed that Anabaena phycocyanin produced inhibition zones against both Bacillus cereus and Staphylococcus aureus (G+) as well as Escherichia coli and Klebsiella pneumonia (G-), while benzyl penicillin was ineffective against the second. The values of IC50 recorded for Anabaena phycocynin were lower than Spirulina phycocyanin and benzyl penicillin. Anabaena phycocyanin (100 μg/ml)-treated cells (B. cereus and K. pneumonia) showed signs of irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged cells or cellular debris and cell wall separation from cell membrane. Anabaena phycocyanin has antibacterial activity, against four pathogenic bacteria, greater than Spirulina phycocyanin or Benzyl Penicillin and other three antibiotics. It exerts its action mainly through affecting the bacterial cell walls and membranes. Industrial relevance: Extending the research work on Anabaena as will expand the library of natural products potentially required in the industrial food sector. Phycocyanins are increasingly required for technological application based on their multiple functionality (e.g.; antioxidant, antimicrobial, food colorant). Anabaena is potentially efficient and economical bio-source for phycocyanin based on and its ubiquity in nature, its ability to fix atmospheric nitrogen and its simple requirements. The specific findings in the work will help specify the technological applications of phycocyanins as food grade preservative in many food systems. Since the results have shown that this new product has antibacterial action comparable to or excelling those of some known antibiotics, it may be a good candidate to be a partial substitute of some antibiotic preparations especially those facing antibacterial resistance from gram- bacteria. Expected new technologies may emerge to introduce this new product into the market with a diversity of applications.