The marine cyanobacterium Trichodesmium spp. forms massive blooms important to carbon and nitrogen cycling in the oceans that often collapse abruptly. We investigated a Trichodesmium bloom in the lagoon waters of New Caledonia to specifically elucidate the cellular processes mediating the bloom decline. We demonstrate physiological, biochemical, and genetic evidence for nutrient and oxidative stress that induced a genetically controlled programmed cell death (PCD) pathway leading to bloom demise.