Due to a rate increase in the resistance of microbial pathogens to currently used antibiotics, there is a need in society for the discovery of novel antimicrobials. Historically, fungi are a proven source for antimicrobial compounds. The main goals of this study were to investigate the fungal diversity associated with sea foam collected around the coast of Prince Edward Island and the utility of this resource for the production of antimicrobial natural products. Obtained isolates were identified using ITS and nLSU rDNA sequences, fermented on four media, extracted and fractions enriched in secondary metabolites were screened for antimicrobial activity. The majority of the isolates obtained were ascomycetes, consisting of four recognized marine taxa along with other ubiquitous genera and many ‘unknown’ isolates that could not be identified to the species level using rDNA gene sequences. Secondary metabolite isolation efforts lead to the purification of the metabolites epolones A and B, pycnidione and coniothyrione from a strain of Neosetophoma samarorum; brefeldin A, leptosin J and the metabolite TMC-264 from an unknown fungus (probably representative of an Edenia sp.); and 1-hydroxy-6-methyl-8-hydroxymethylxanthone, chrysophanol and chrysophanol bianthrone from a Phaeospheria spartinae isolate. The biological activity of each of these metabolites was assessed against a panel of microbial pathogens as well as several cell lines.