Late in summer 2003, extensive mass mortality of at least 25 rocky benthic macro-invertebrate species (mainly gorgonians and sponges) was observed in the entire Northwestern (NW) Mediterranean region, affecting several thousand kilometers of coastline. We were able to characterize the mortality event by studying six areas covering the main regions of the NW Mediterranean basin. The degree of impact on each study area was quantified at 49 sites by estimating the proportion of colonies affected in populations of several gorgonian species compared with reference data obtained in years without mortality signs. According to these data, the western areas (Catalan coast and Balearic Islands) were the least affected, while the central areas (Provence coast and Corsica-Sardinia) showed a moderate impact. The northernmost and eastern areas (Gulf of Genoa and Gulf of Naples) displayed the highest impact, with almost 80% of gorgonian colonies affected. The heat wave of 2003 in Europe caused an anomalous warming of seawater, which reached the highest temperatures ever recorded in the studied regions, between 1 and 3 °C above the climatic values (mean and maximum). Because this exceptional warming was observed in the depth ranges most affected by the mortality, it seems likely that the 2003 anomalous temperature played a key role in the observed mortality event. A correlation analysis between temperature conditions and degree of impact seems to support this hypothesis. Under the present climate warming trend, new mass mortality events may occur in the near future, possibly driving a major biodiversity crisis in the Mediterranean Sea.