Investigations of how species compositional changes interact with other aspects of global change, such as nutrient mobilization, to affect ecosystem processes are currently lacking. Many studies have shown that mixed species plant litters exhibit non-additive effects on ecosystem functions in terrestrial and aquatic systems. Using a full-factorial design of three leaf litter species with distinct initial chemistries (carbon:nitrogen; C:N) and breakdown rates (Liriodendron tulipifera, Acer rubrum and Rhododendron maximum), we tested for additive and non-additive effects of litter species mixing on breakdown in southeastern US streams with and without added nutrients (N and phosphorus). We found a non-additive (antagonistic) effect of litter mixing on breakdown rates under reference conditions but not when nutrient levels were elevated. Differential responses among single-species litters to nutrient enrichment contributed to this result. Antagonistic litter mixing effects on breakdown were consistent with trends in litter C:N, which were higher for mixtures than for single species, suggesting lower microbial colonization on mixtures. Nutrient enrichment lowered C:N and had the greatest effect on the lowest- (R. maximum) and the least effect on the highest-quality litter species (L. tulipifera), resulting in lower interspecific variation in C:N. Detritivore abundance was correlated with litter C:N in the reference stream, potentially contributing to variation in breakdown rates. In the nutrient-enriched stream, detritivore abundance was higher for all litter and was unrelated to C:N. Thus, non-additive effects of litter mixing were suppressed by elevated streamwater nutrients, which increased nutrient content of all litter, reduced variation in C:N among litter species and increased detritivore abundance. Nutrients reduced interspecific variation among plant litters, the base of important food web pathways in aquatic ecosystems, affecting predicted mixed-species breakdown rates. More generally, world-wide mobilization of nutrients may similarly modify other effects of biodiversity on ecosystem processes.