Environmental stressors, such as climate fluctuations, and anthropogenic stressors, such as fishing, are of major concern for the management of deep-sea ecosystems. Deep-water habitats are limited by primary productivity and are mainly dependent on the vertical input of organic matter from the surface. Global change over the latest decades is imparting variations in primary productivity levels across oceans, and thus it has an impact on the amount of organic matter landing on the deep seafloor. In addition, anthropogenic impacts are now reaching the deep ocean. The Mediterranean Sea, the largest enclosed basin on the planet, is not an exception. However, ecosystem-level studies of response to varying food input and anthropogenic stressors on deep-sea ecosystems are still scant. We present here a comparative ecological network analysis of three food webs of the deep Mediterranean Sea, with contrasting trophic structure. After modelling the flows of these food webs with the Ecopath with Ecosim approach, we compared indicators of network structure and functioning. We then developed temporal dynamic simulations varying the organic matter input to evaluate its potential effect. Results show that, following the west-to-east gradient in the Mediterranean Sea of marine snow input, organic matter recycling increases, net production decreases to negative values and trophic organisation is overall reduced. The levels of food-web activity followed the gradient of organic matter availability at the seafloor, confirming that deep-water ecosystems directly depend on marine snow and are therefore influenced by variations of energy input, such as climate-driven changes. In addition, simulations of varying marine snow arrival at the seafloor, combined with the hypothesis of a possible fishery expansion on the lower continental slope in the western basin, evidence that the trawling fishery may pose an impact which could be an order of magnitude stronger than a climate-driven reduction of marine snow.