Ponds play an important role in processing and decomposing plant litter inputs from both, allochthonous and autochthonous sources, contributing in turn to the carbon cycling on Earth. In Mediterranean regions, ponds are highly vulnerable because they suffer from two major impacts related to anthropogenic stress: pollution and climate change effects, such as drought, which both may affect litter decomposition. The aim of this project was to quantify the potential microbial litter decomposition in Mediterranean ponds and to identify the main drivers for their variability, to be able to predict changes in litter decomposition potential under global change. We measured litter decomposition potential in 30 ponds, which are located in areas under different human pressure (pond status categories: low, medium and high) and water intermittency (permanent and temporary ponds), during three sampling periods. We used the tea-bag index approach, incubating the standardized organic substrates for approximately 80 days measured the main environmental variables. We did not find significant differences in the percentage of organic matter among pond status categories. However, temporary ponds tended to have less organic matter loss in comparison to permanent ponds. Decomposition rates were influenced by water temperature and environmental gradients (e.g. nutrient concentrations). Our work contributes to disentangling the main drivers of organic matter decomposition in Mediterranean ponds, which is key to understanding of anthropogenic stress and climate change effects in these ecosystems.