Background Litter decomposition is a fundamental process of biogeochemical cycles, and there is a strong consensus that litter mixture interactions are one of the factors driving the decomposition process. A better understanding of how climate change can alter interactions between species and the litter decomposition process could facilitate projections of ecosystem functioning into the future. Methods A 24-month litterbag decomposition experiment was carried out in a Mediterranean forest to analyze the effects of climate and species diversity changes on litter mixture interactions and the decomposition process. Results In the control plot, synergistic interactions increased with time and species diversity in litter mixtures, leading to more efficient litter decomposition. Drier conditions obtained in the field with a rain exclusion device decreased decomposition rates, resulting in three-fold less synergistic interactions and five-fold more antagonistic interactions during the decomposition process. Furthermore, synergistic interactions were better preserved in the drought conditions with increasing number of species. Conclusions Our findings underline how a longer drought season could strongly affect the relationship between biodiversity and ecosystem functioning. Drier climate led to slower mass loss rates and a strong shift in the litter mixture interactions, with fewer synergistic interactions and more antagonistic interactions.