This work investigated the microbial toxicity of soluble species that can potentially be leached from the II–VI semiconductor materials, cadmium telluride and cadmium selenide. The soluble ions tested included: cadmium, selenite, selenate, tellurite, and tellurate. Their toxicity towards the acetoclastic and hydrogen-consuming trophic groups in a methanogenic consortium as well as towards a bioluminescent marine bacterium, Aliivibrio fischeri (Microtox® test), was assessed. The acetoclastic methanogenic activity was the most affected as evidenced by the low 50% inhibiting concentrations (IC50) values obtained of 8.6 mg L−1 for both cadmium and tellurite, 10.2 mg L−1 for tellurate, and 24.1 mg L−1 for selenite. Both tellurium oxyanions caused a strong inhibition of acetoclastic methanogenesis at low concentrations, each additional increment in concentration provided progressively less inhibition increase. In the case of the hydrogenotrophic methanogenesis, cadmium followed by selenite caused the greatest inhibition with IC50 values of 2.9 and 18.0 mg L−1, respectively. Tellurite caused a moderate effect as evidenced by a 36.8% inhibition of the methanogenic activity at the highest concentration tested, and a very mild effect of tellurate was observed. Microtox® analyses showed a noteworthy inhibition of cadmium, selenite, and tellurite with 50% loss in bioluminescence after 30 min of exposure of 5.5, 171.1, and 458.6 mg L−1, respectively. These results suggest that the leaching of cadmium, tellurium and selenium ions from semiconductor materials can potentially cause microbial toxicity.