Host-specific mortality driven by natural enemies is a widely discussed mechanism for explaining plant diversity. In principle, populations of plant species can be regulated by distinct host-specific natural enemies that have weak or nonexistent effects on heterospecific competitors, preventing any single species from becoming dominant and thus promoting diversity. Two of the first steps in exploring the role of natural enemies in diversity regulation are to (1) identify potential enemies and (2) evaluate their levels of host specificity by determining if interactions between any one host and its enemy have equivalent survival impacts on co-occurring host species. We developed a bioinformatics framework to evaluate impacts of potential pathogens on seedling survival, for both single and multiple infections. Importantly, we consider scenarios not only if there are specialist pathogens for each plant, but also when generalist pathogens have differential effects on multiple host species, and when co-infection has species-specific effects. We then applied this analytical framework to a field experiment using molecular techniques to detect potential fungal pathogens on co-occurring tree seedling hosts. Combinatorial complexity created by 160 plant-fungus interactions was reduced to eight combinations that affect seedling survival. Potential fungal pathogens had broad host ranges, but seedling species were each regulated by different combinations of fungi or by generalist fungi that had differential effects on multiple plant species. Soil moisture can have the potential to shift the nature of the interactions in some plant-fungal combinations from neutral to detrimental. Reassessing the assumption of single-enemy-single-host interactions broadens the mechanisms through which natural enemies can influence plant diversity.