Within the overwhelming increase of pollutants spilled into the sea, heavy metals are emerging contaminants due to their high toxicity, persistence, and accumulation in both the organisms and the environment. This study aims to assess the retention capability of lead and cadmium by the sponge Axinella damicornis under laboratory conditions. The sponges were exposed for 144 h to seawaters artificially polluted with Pb and Cd separately and with a mixture of the two metals. The retention efficiency of the sponge in removing the metals from seawater and the metal uptake in the sponge body at the end of the experiment were measured. The highest values were recorded for Pb: in the sponge, this metal resulted in 6 times and 9 times more concentrated than Cd, in the case of single and double contamination respectively. The metal concentrations, especially for Pb, were much higher in A. damicornis than in other organisms investigated in the sea. The synergistic effects of the mixture of Pb and Cd were also evaluated, and remarkable signs of stress and necrosis were recorded in the specimens exposed to the two metals combined. This study paves the way to the knowledge increasing on both the effective effects of heavy metal contamination on the organisms and on the possible use of A. damicornis as efficient tool for bioremediation of polluted seawaters.