Periodically, the marine cyanobacterium Leptolyngbya crossbyana forms extensive blooms on Hawai'ian coral reefs and results in significant damage to the subtending corals. Additionally, corals near mats of this cyanobacterium, but not directly overgrown, have been observed to undergo bleaching. Therefore, samples of this cyanobacterium were chemically investigated for bioactive secondary metabolites that might underlie this toxicity phenomenon. (1)H NMR spectroscopy-guided fractionation led to the isolation of four heptabrominated polyphenolic ethers, crossbyanols A-D (1-4). Structure elucidation of these compounds was made challenging by their very low proton to carbon (H/C) ratio, but was completed by combining standard NMR and MS data with 2 Hz-optimized HMBC data. Derivatization of crossbyanol A as the diacetate assisted in the assignment of its structure. Crossbyanol B (2) showed antibiotic activity with an MIC value of 2.0-3.9 microg/mL against methicillin-resistant Staphylococcus aureus (MRSA) and relatively potent brine shrimp toxicity (IC(50) 2.8 ppm).