Cladophora mats that accumulate and decompose along shorelines of the Great Lakes create potential threats to the health of humans and wildlife. The decaying algae create a low oxygen and redox potential environment favoring growth and persistence of anaerobic microbial populations, including Clostridium botulinum, the causal agent of botulism in humans, birds, and other wildlife. In addition to the diverse population of microbes, a dynamic chemical environment is generated, which involves production of numerous organic and inorganic substances, many of which are believed to be toxic to the sand and aquatic biotic communities. In this study, we used 16S-rDNA-based-amplicon sequencing and microfluidic-based quantitative PCR approaches to characterize the bacterial community structure and the abundances of human pathogens associated with Cladophora at different stages (up to 90 days) of algal decay in laboratory microcosms. Oxygen levels were largely depleted after a few hours of incubation. As Cladophora decayed, the algal microbial biodiversity decreased within 24 h, and the mat transitioned from an aerobic to anaerobic environment. There were increasing abundances of enteric and pathogenic bacteria during decomposition of Cladophora, including Acinetobacter, Enterobacter, Kluyvera, Cedecea, and others. In contrast, there were no or very few sequences (