Mass spectrometry-guided isolation of the lipophilic extract of Trichodesmium bloom material led to the isolation and structure characterization of a new thiazole-containing di-chlorinated polyketide (1). The structure of 1 was deduced using 1D and 2D NMR analysis, high-resolution mass spectrometry analysis and complementary spectroscopic procedures. Trichothiazole A possesses interesting structural features, such as a terminal alkyne, two vinyl chlorides and a 2,4disubstituted thiazole. Trichothiazole A showed moderate cytotoxicity to Neuro-2A cells (EC 50 : 13.3 ± 1.1 μM).